1
1
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
https://revistascientificas.uach.mx/index.php/tecnociencia
ISSN-e: 2683-3360
Literature review paper
Bioactive compound production via solid-state
fermentation: emerging opportunities
Producción de compuestos bioactivos mediante fermentación en
estado sólido: oportunidades emergentes
* Correspondence Author: e-mail: itza.cordero@itdurango.edu.mx (Itza Nallely Cordero Soto)
DOI: https://doi.org/10.54167/tch.v20i1.2152
Received: November 14, 2025; Accepted: Febuary 19, 2026
Published by the Autonomous University of Chihuahua, through the Research and Postgraduate Department.
Section Editor: Dr. Armando Quintero-Ramos
Abstract
The natural environment is an extraordinary reservoir of microorganisms that generate compounds
with significant pharmaceutical relevance. Over the past decades, numerous companies have
successfully exploited these microorganisms, primarily through submerged fermentation, to obtain
antibiotics, enzymes, and other bioactive molecules. However, submerged fermentation sometimes
presents limitations regarding oxygen transfer, production yields, compound stability, foaming, and
environmental impact. Solid-state fermentation is a more sustainable alternative technology because
it can valorize agro-industrial byproducts as culture media and produce bioactive compounds,
contributing to a circular bioeconomy. The pharmaceutical industry is seeking solutions to decrease
the costs of production processes and enhance process sustainability, and solid-state fermentation
Luisa Marcela Valdés-Velasco1,2, Quentin Carboué1, Ernesto Favela-Torres3, Sergio Huerta-
Ochoa3, Itza Nallely Cordero-Soto4*
1 Agro-Biotechnologies Industrielles (ABI), CEBB, AgroParisTech, 3 Rue des Rouges-Terres, 51110,
Pomacle, France
2Fundación de Estudios Superiores Monseñor Abraham Escudero Montoya FUNDES, Carrera 7 N° 10-37
Barrio Centro, 733520, Espinal, Colombia
3Universidad Autonoma Metropolitana, Department of Biotechnology, Iztapalapa Unit, 186 San Rafael
Atlixco Avenue, Colonia Vicentina, 09340, Mexico City, Mexico
4Tecnológico Nacional de México/Instituto Tecnológico de Durango, Departamento de Ingenierías
Química-Bioquímica, Laboratorio Nacional CONAHCYT de Evaluación de Productos Bióticos
(LaNAEPBi), Boulevard Felipe Pescador 1830 Oriente. Colonia Nueva Vizcaya, 34180, Durango, México.
2
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
may provide exciting alternatives. However, challenges remain in scaling up, process control, and
optimizing the recovery of bioactive compounds. This review highlights advances in bioactive
compounds with potential pharmaceutical applications produced through solid-state fermentation,
with particular emphasis on different classes, including antibiotics, biosurfactants, enzymes,
polymers, vitamins, and aroma compounds. By addressing current limitations and showcasing
innovative applications, solid-state fermentation is positioned as a viable complementary strategy
for pharmaceutical bioprocesses.
Keywords: pharmaceutical industry, biological activity, byproducts, valorization, microbial
compounds.
Resumen
El entorno natural constituye una valiosa fuente de microorganismos capaces de producir
compuestos de gran relevancia farmacéutica. Durante las últimas décadas, numerosas empresas han
aprovechado estos microorganismos, principalmente mediante fermentación sumergida, para
obtener antibióticos, enzimas y otras moléculas bioactivas. Sin embargo, este sistema de
fermentación presenta limitaciones asociadas a la transferencia de oxígeno, los bajos rendimientos
de producción para algunos compuestos y su estabilidad, la formación de espuma durante el proceso
y su impacto ambiental. En este contexto, la fermentación en estado sólido surge como una
alternativa más sostenible, ya que permite valorizar subproductos agroindustriales como sustratos
y producir compuestos bioactivos, favoreciendo así el desarrollo de una bioeconomía circular. Dado
que la industria farmacéutica busca reducir los costos y aumentar la sostenibilidad de sus procesos,
esta tecnología ofrece oportunidades prometedoras. No obstante, aún existen desafíos importantes
en cuanto a la escalabilidad, el control del proceso y la optimización de la recuperación de los
compuestos producidos. Esta revisión presenta los avances importantes en la obtención de
compuestos bioactivos con potencial aplicación farmacéutica mediante fermentación en estado
sólido, con especial atención a diversas clases de productos, como antibióticos, biosurfactantes,
enzimas, polímeros, vitaminas y compuestos aromáticos. Al analizar las limitaciones actuales y
destacar aplicaciones emergentes, se posiciona a la fermentación en estado sólido como una
estrategia complementaria y viable para el desarrollo de bioprocesos farmacéuticos más sostenibles.
Palabras clave: industria farmacéutica, actividad biológica, subproductos, valorización,
compuestos microbianos.
1. Introduction
Over the centuries, pharmaceuticals have provided many health benefits and improved the
quality of human life. They consist of a large and varied group of organic compounds used for their
specific biological effects. They penetrate cellular membranes, have a specific mode of action, and can
persist in the body. Many pharmaceuticals, such as analgesics, antibiotics, antiepileptics, β-blockers,
blood-lipid regulators, antidepressants, anxiolytics, sedatives, contraceptives, steroidal hormones,
antineoplastics, and antitumor agents, have been produced and sold worldwide (Salehi &
Rashidinejad et al., 2025). The pharmaceutical sector is one of the fastest-growing industries, with a
global market worth over a trillion USD (Brekke et al., 2025).
3
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Biotechnology has improved the production of biological pharmaceuticals in the market, such as
monoclonal antibodies (e.g., trastuzumab deruxtecan), cytokines, fusion proteins, therapeutic
enzymes, recombinant vaccines, blood factors, hormones, and growth factors (Inoue et al., 2020). The
above statement can be associated with products that show advantages over synthetic drugs, such as
better selectivity, lower toxicity, milder side effects, and being more environmentally friendly (Inoue
et al., 2020). Generally, the microbial bioactive compounds are produced by submerged fermentation
(SmF), such as steroids (prednisolone, 11-α-hydroxy-progesterone), intermediate compounds (citric
acid, fumaric acid), antibiotics (penicillin, cephalosporin, cordycepin), antifungals (polynes),
antivirals (Shikimic acid (precursor of oseltamivir), and antiparasitic (avermectins) (Ma et al., 2023).
Many studies have highlighted higher yields of bioactive production when solid-state fermentation
(SSF) is involved (Kumar et al., 2021), which can be attributed to more significant biomass growth
and oxygen availability. For instance, the commercial production of statins and related substances
prefers SSF because of its low media cost, product stability, increased product yield, and increased
porosity (Valdés-Velasco et al., 2022).
The trends in scientific research papers and patent documents on solid-state fermentation in
pharmaceutical applications are as follows. Research papers were searched in the Scopus® database
(www.scopus.com) containing the words (solid AND state AND fermentation AND pharmaceutical
or health or pharmacy or medical) in the title, abstract, or keywords, from 2014 to present, resulting
in 772 documents. A huge linear increasing trend was observed for the number of papers. The
increase was about 75 %. Patent documents were searched in the Lens database (www.lens.org)
containing the words (solid AND state AND fermentation AND pharmaceutical) in the keyword or
patent field from 2014 to 2024. Around 39851 patent records were found. Therefore, there has been
growing interest in this topic over the last 10 years.
This review focuses on bioactive compounds obtained through a specific fermentation technique,
SSF, which has shown higher product yields using low-cost substrates than submerged fermentation
does. The generalities, benefits, and challenges of the SSF are described in Section 2. Bioactive
compounds, including antibiotics, aromas, biosurfactants, polymers, enzymes and vitamins, and
their related SSF production are presented in Section 3. Finally, Section 4 presents the conclusions
and perspectives of this review.
2. Benefits and challenges of solid-state fermentation
SSF is a microbial culture technique involving the growth of microorganisms on a solid
medium in the absence or near absence of free water runoff (Cordero Soto et al., 2025). Water plays
an essential role in biological processes, and is absorbed into solid surfaces, where it can be present
in the form of a thin film (Valdés-Velasco et al., 2022). Fermentation of solid materials is an ancient
technology that has been used since antiquity to produce food. It is widely used in East Asian
countries to prepare food on an industrial scale. In contrast, SmF is the preferred for the industrial
production of microbial value-added compounds in the West (Cordero Soto et al., 2025). The main
reason for this is the heterogeneous nature of the solid medium, which impedes the efficient
monitoring of the process, such as temperature, pH, moisture, and substrate concentration, whereas
SmF has precise online monitoring devices.
4
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
SSF holds tremendous potential for producing microbial compounds compared to SmF. The main
advantage of SSF is the possibility of using agro-industrial byproducts as a solid medium. These
byproducts are massively overproduced worldwide and still contain an exciting level of nutrients
that enable microbial growth (Chilakamarry et al., 2022; Tripathi et al., 2024). The valorization of
these wastes through SSF increases the sustainability of the process. From an economic perspective,
their use lowers global costs because they are inexpensive, whereas synthetic carbon and nitrogen
sources account for a substantial part of the worldwide cost (Costa et al., 2021). Regarding the
environmental aspect, this valorization mitigates the negative impact on the environment that may
otherwise result from improper waste management, especially in the case of byproducts containing
toxic compounds (Mahanta et al., 2008). Finally, this aligns with increasing public expectations
regarding the natural origin of products, whether related to the health, cosmetics, or food industries
(Cordero Soto et al., 2025).
Regarding raw materials, the requirement for SSF is usually lower, leading to a cheaper initial
investment. In addition, low water content usually causes the SSF bioprocesses to have lower surface
area occupation and does not require downstream effluent treatment, which impacts the overall cost
(Valdés-Velasco et al., 2022). This is always the case, as some SSF processes for enzyme production
may require the same amount of water to extract the enzyme, which can be similar to the total water
content used in SmF processes. Table 1 presents the main advantages and disadvantages of solid-
state fermentation (SSF) and submerged fermentation (SmF) for the production of bioactive
compounds.
Table 1. Comparison between Solid-State Fermentation and Submerged Fermentation.
Tabla 1. Comparación entre la fermentación en estado sólido y la fermentación sumergida.
Solid-State Fermentation
Submerged Fermentation
Reference
Limited; difficult control of temperature, pH,
and oxygen
High; easy monitoring and control of
pH, temperature, and aeration
Cordero Soto et
al., 2025
Generally suitable for aerobic
microorganisms, but difficult to regulate
Efficient and controllable through
agitation and aeration
Mehmood et al.,
2022
Low
High
Generally lower
Higher due to equipment, energy use,
and process control
More complex and limited at industrial scale
High; widely applied at industrial
scale
Lower due to low water activity
Higher due to liquid medium
More complex; requires additional
downstream steps
Easier through filtration or
centrifugation
2.1 Oxygen
The reduced availability of free water in SSF enhances oxygen transfer, thereby promoting
microbial growth (Banat et al., 2021; Valdés-Velasco et al., 2022). Oxygen transfer depends on the
5
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
available interfacial gas-liquid surface area and the thickness of the wet fungal layer. Besides, SSF
describes resistance to phenomena of catabolite repression and substrate inhibition. Hence, enzymes
are usually produced in higher yields than those observed in SmF using elevated concentrations of
simple sugars with relatively low levels of inducers (Valdés-Velasco et al., 2022).
Despite these benefits, substrate uptake and biomass quantification are challenging because of the
close interaction between microorganisms and the solid medium, although indirect methods such as
respirometry monitoring for biomass determination may be used.
2.2 Temperature
Another aspect of the solid substrate is its porosity and the formation of mass and heat
gradients due to the poor transfer coefficients of the solid matrix, which may lead to the accumulation
of heat and gases inside the bioreactor bed, especially at higher production scales (Cordero Soto et
al., 2025).
Heat transfer is important because microorganisms often grow in specific temperature ranges, and
the fermentation process generates metabolic heat. Different strategies exist to overcome this issue,
resulting in a wide diversity of bioreactor designs (Krishania et al., 2018). Two main strategies exist
that can be used in combination. The first strategy is based on the forced aeration of moist air through
the bed to remove heat, carbon dioxide, and volatile substances through convection (Mehmood et al.,
2022). In addition, the water evaporation process, an endergonic reaction, allows efficient heat
removal but requires water replenishment, which can be carried out through aeration with water-
saturated air (Mehmood et al., 2022). Granulometry and the compressibility index are also key
parameters for enhancing the heat transfer (Oiza et al., 2022). The other strategy is agitation, which
can release nutrients and impair the formation of gradients, but can disrupt microbial cells, especially
in the case of filamentous microorganisms. These damages can be mitigated by modulating
parameters such as the frequency and speed of agitation and the type of agitation system, that is,
baffles, padded, or rotating drum (Robinson & Nigam, 2003; Finkler et al., 2017). Thus, for each
agitated bioprocess, a careful study of the impacts of these parameters must be conducted to achieve
a balance between mass and heat transfer gradients and cell disruption. Recent advances in
mathematical modeling have led to a deeper understanding of SSF processes and may support the
successful development and large-scale implementation of SSF production systems (Perez et al., 2019;
Finkler et al., 2021).
2.3 Recovery of biomass and products
Downstream processes account for 70 % of the total production cost. They are not required if
the fermented solid is used as a final product, such as conidia, for applications such as pesticides.
Thus, bioprocesses have taken advantage of the economic benefits of SSF. However, if they are
required, the use of solvents is common and sometimes not environmentally friendly, limiting the
pharmaceutical applications of the obtained bioactive compounds and the reuse of solid waste. In
addition, solvents can increase the production cost because of the high required volume, their prices,
and energy consumption (Oiza et al., 2022). Bioproduct recovery depends on its physical and
chemical characteristics, such as thermostability and pH resistance. Thus, alternative methods for
bioproduct recovery with reduced environmental and economic impact include ultrasound-assisted
6
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
extraction, microwave-assisted extraction, supercritical fluid extraction, solid-liquid extraction,
pressurized liquid extraction, subcritical water extraction, solid-solid extraction, and enzyme-
assisted extraction (Oiza et al., 2022). However, optimization focused on downstream processes has
not been widely studied and is fundamental to the total production cost and environmental impact
of SSF.
3. Bioactive compounds obtained by solid-state fermentation
Microbial diversity is a tremendous source of bioactive compounds whose applications range
from antimicrobial, antioxidant, and immunomodulatory activities in various critical industries like
drugs, healthcare, surgical devices, food preservation, and packaging, to name a few. In the specific
case of antimicrobial activities against pathogenic agents, and notably because of the appearance of
resistant pathogenic strains to systemic antibiotics, the search for new antimicrobial compounds is of
primary importance in the chemistry and biotechnology sectors (Varghese et al., 2020). In this context,
the focus has been on antibiotics, biosurfactants, polymers, aromas, enzymes, and vitamins (table 2).
3.1 Antibiotics
Antibiotics are biologically active compounds produced by microorganisms as a defense
mechanism to stop or selectively inhibit the growth of other microorganisms. Antibiotic production
has been investigated in the last decades using alternative economic sources, such as agro-industrial
byproducts, using SmF and SSF (De la Cruz-Quiroz et al., 2019; Zeng et al., 2022). Several factors
must be considered, including environmental and biological aspects, physiological characteristics of
the microorganisms, and their optimal growth culture (De la Cruz-Quiroz et al., 2019).
Cephalosporin-C (Fig. 1A) was produced in comparable quantities as a secondary metabolite through
SSF and SmF. In the case of SSF, sugarcane bagasse was used as a solid medium (Tabaraie et al., 2012).
Other studies have reported antibiotic production by SSF, such as the extracellular antibiotic
rifamycin B (Fig. 1B), produced by Amycolatopsis Mediterranean MTCC 14 from agro-industrial
byproducts (Vastrad & Neelagund, 2012). The results of this study showed that ground nutshells and
coconut oil cake presented higher yields of antibiotic production than those obtained with groundnut
oil cake and rice husks. Paromomycin (Fig. 1C) is an effective antibiotic for treating Gram-positive
and Gram-negative bacteria, protozoa, mycobacteria, and numerous antibiotic-resistant pathogens.
It is produced by Streptomyces rimosus subsp. paromomycinus NRRL 2455 through SSF using corn bran
impregnated with aminoglycosides as the growth medium (El-Housseiny et al., 2021). Cephamycin
C antibiotic production by Nocardia lactamdurans was evaluated in SSF using soybean flour with a
moisture content of 65 % at 28 °C and an initial pH of 6.5. The maximum cephamycin C production
under these conditions was 15.75 mg (g dry solid)-1 (Kagliwal et al., 2009). Henceforth, a gram of dry
solid (gds). Other necessary antibiotics produced as secondary metabolites during fermentation
include penicillin, neomycin, puromycin, cephabacin, nocardicin A, actinorhodin, enterocin,
tetracenomycin, actinomycin, carbomycin, erythromycin, and tetracycline (Kumar et al., 2021; Zeng
et al., 2022).
Antibiotic production by biotechnological processes, such as SSF, generally involves the use of a
complex medium that may decrease the overall purity of the compound. However, extraction and
7
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
purification strategies to obtain high-grade metabolites have been continuously studied to overcome
this limitation.
Figure. 1 Chemical structures of antibiotics produced by SSF. A) Cephalosporin-C. B) Rifamycin B. C)
Paramomycin. D) Cephamycin C.
Figura. 1 Estructuras químicas de antibióticos producidos por SSF. A) Cefalosporina C. B) Rifamicina B. C)
Paromomicina. D) Cefamicina C.
3.2 Aroma compounds
Aroma compounds are molecules naturally obtained from plants, seeds, and fruits, or
through biotechnological processes using microorganisms or isolated enzymes. Their natural
production has been strongly performed in the last two decades developing fermentation systems,
mainly by SmF (Cordero-Soto et al., 2025). Nevertheless, other approaches, such as SSF, have been
proposed for by-product valorization and aroma production (Hadj Saadoun et al., 2021), especially
those showing novel applications in the pharmaceutical industry and medical treatments (Arya et
al., 2021).
The natural aldehyde 4-hydroxy-3-methoxybenzaldehyde (Fig. 2A) is the main compound in the
extract obtained from the pods of the Vanilla planifolia orchid (Arya et al., 2021). This compound,
named vanillin, has a sweet flavor and delicate floral fragrance, properties that the food and cosmetic
industries have been searching for to increase the quality of their products (Palmerín-Carreño et al.,
2019). However, in the last decades, its medicinal and biological properties have been investigated
(Arya et al., 2021). Vanillin exhibits antioxidant, anticarcinogenic, anti-inflammatory, anti-apoptotic,
neuroprotective, and anti-stress biological activities (Ueno et al., 2019). The consumption of vanillin
in a designed high-fat diet for obese mice revealed promising results in reducing adipose tissue and
glucose metabolism, among other benefits (Martău et al., 2021). In addition to its intake, vanillin has
also been studied in alternative medicine and aromatherapy to elucidate its neuropsychological
effects (Ueno et al., 2019).
8
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
With these novel applications and the high global demand for vanillin, efforts to obtain this
compound through biotechnological processes have increased, as its direct extraction from plants is
limited, and the vanillin obtained by microbial/enzymatic bioprocesses is considered a safe and
natural source (Martău et al., 2021; Paul et al., 2021). In this sense, recent studies have been carried
out by SSF to produce biovanillin. Mehmood et al. (Mehmood, Ahmed, et al., 2022) studied fruit
byproducts with a high content of ferulic acid, including pomegranate, banana, and orange peels as
substrates to produce biovanillin using Enterobacter hormaechei, reaching a maximum yield of 0.09 mg
g-1 after 24 h of fermentation. Other food byproducts, such as sugarcane bagasse, wheat straw, corn
cob, and rice bran and straw, were evaluated and selected according to their ferulic acid content and
biovanillin production by SSF (Mehmood, Saleem, et al., 2022). The results showed that sugarcane
bagasse is a promising substrate for producing biovanillin using Enterobacter hormaechei at 37.5 °C,
pH 7.5, and a moisture content of 70 %.
Phenethyl alcohol (Fig. 2B), also known as 2-Phenylethanol (2-PE), is a higher alcohol with pleasant
rose-like notes naturally found in plants and flowers. It is used in the pharmaceutical, cosmetic, and
food industries as a preservative because of its efficient antimicrobial and antifungal activities
(Martínez et al., 2018; Mierzejewska et al., 2019). 2-PE has been studied as an anti-depressant and
anti-stress treatment through inhalation in mice (Ueno et al., 2019). Its biotechnological production
has been mainly studied in SmF, especially by coupling in situ product removal techniques to avoid
the inhibition of microorganisms. However, other approaches have been explored, such as using food
byproducts to valorize or decrease the production costs (Martínez et al., 2018; Martínez-Avila et al.,
2021). Soy fiber, rice husk, rice fiber, and apple pomace were evaluated as potential substrates for 2-
PE bioconversion through SSF using Pichia kudriavzevii. Results showed that the highest 2-PE
production (25.2 mg gds-1) was obtained using red apple pomace as the substrate with L-
phenylalanine (L-Phe) supplementation after 70 h (Martínez-Avila et al., 2021). The potential of
sugarcane bagasse as a single carbon source, supplemented with L-phe, using Pichia kudriavzevii in
an SSF process was evaluated and optimized, reaching a maximum 2-PE concentration of 27. 2 mg
gds-1 (Martínez-Avila et al., 2020). Moreover, sugarcane bagasse was evaluated in SSF to produce 2-
PE and its derivative ester, 2-phenethyl acetate (2-PEA) (Fig. 2C), a compound with similar properties
and aroma (Martínez et al., 2018). L-phe was added to the media to trigger the Ehrlich pathway in
Kluyveromyces marxianus yeast. The results showed that the system was adequate for producing 2- PE
and its ester, 2-PEA ester (Martínez et al., 2018). Fig. 3 illustrates the mechanism for obtaining 2-PE
and its ester, 2-PEA.
2-phenethyl acetate and several fruity aroma compounds, such as isoamyl acetate, decanoate, ethyl
dodecanoate, and octanoate, were produced by Saccharomyces cerevisiae in SFF from orange peels
(Mantzouridou et al., 2015). Lactones have also been obtained using SFF. Try et al. (2018) proposed a
novel system based on an impregnated inert support (luffa sponge) using Yarrowia lipolytica; the
results showed a high yield of 3-hydroxy-γ- decalactone (Fig. 2D). However, the biological activity
and medicinal potential of these aroma compounds have been poorly studied, and their study has
focused on their application as flavoring agents.
9
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Fig. 2 Chemical structures of aromas produced by SSF. A) Vanillin. B) 2-Phenylethanol. C) 2-Phenethyl acetate.
D) 3-hydroxy-γ- decalactone.
Fig. 2 Estructuras químicas de aromas producidos por SSF. A) Vainillina. B) 2-feniletanol. C) Acetato de 2-
feniletilo. D) 3-hidroxi-γ-decalactona.
Fig. 3 Ehrlich pathway to produce 2-Phenylethanol and 2-phenylethylacetate.
Fig. 3 Ruta de Ehrlich para la producción de 2-feniletanol y 2-feniletil acetato.
3.3 Biosurfactants
Biosurfactants are amphiphilic compounds that reduce surface tension. Bacteria, yeasts, and
fungi produce these compounds, with no reported side effects in humans (Wan et al., 2022). Their
environmental toxicity is lower, and their resistance to extreme temperatures, pH, and salinity is
higher than that of chemical surfactants (Ribeiro et al., 2020). A critical contemporary biological
activity of biosurfactants is the inactivation of SARS-CoV2 by membrane disruption (Banat et al.,
2021; Raza et al., 2022). However, large-scale biosurfactant synthesis is limited by its high production
costs and low productivity (Banat et al., 2021). For instance, sophorolipids, one of the cheapest
biosurfactants in the market, have a sales price estimated at approximately 32 USD Kg-1 versus 1-2
USD Kg-1 for a synthetic surfactant such as sodium lauryl sulfate (Dolman et al., 2019). Therefore,
different strategies have been proposed to improve production, including the use of SSF. Indeed, in
the case of lipopeptide synthesis, for example, a study showed that SSF, in comparison with SmF,
10
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
increased the production tenfold according to the evaluated strains compared to gL-1 (Valdés-Velasco
et al., 2022). Moreover, because of the absence or near absence of free water, foam formation can be
significantly reduced, which is an issue during biosurfactant production using SmF (Chen et al.,
2021). Foaming may hinder the overall productivity of the process, requiring the addition of
expensive antifoaming agents (Valdés-Velasco et al., 2022). The use of agro-industrial byproducts in
SSF presents new challenges in downstream purification owing to the complex nature of the crude
extract (Valdés-Velasco et al., 2022). Therefore, using an inert support such as polyurethane foam
with an impregnated nutritional solution avoids these problems, facilitating product analysis,
purification, control, and monitoring of the bioprocess (Jiménez-Peñalver et al., 2019). This strategy
has been successfully used for glycolipid and lipopeptide production in SSF (Gong et al., 2020;
Valdés-Velasco et al., 2022).
Biosurfactants are classified according to their structure into glycolipids, lipopeptides,
phospholipids, polymerics, and particulates. Glycolipids have potential applications in the
pharmaceutical industry because of their antimicrobial, anti-adhesive, antitumor, antioxidant,
antiviral, immunomodulatory, enzyme-inhibitory, and insecticide effects (Varvaresou & Iakovou,
2015; Banat et al., 2021). Sophorolipids and rhamnolipids are representative glycolipid biosurfactants.
Several studies have reported the production of sophorolipids (Fig. 4A) by SSF using agro-industrial
residues as solid supports (Jiménez-Peñalver et al., 2019). For instance, sophorolipids produced by
Starmerella bombicola (previously Candida bombicola) using a mixture of sunflower oil cake and crude
soybean oil reached a yield of 0.5 g gds-1 and exhibited activity against cancerous cells in human
tumor cell lines of hepatocellular carcinoma HepG2 and lung cancer A549 by inhibiting the activities
of urokinase and histone deacetylase (Rashad et al., 2014). Candida bombicola NRRL Y-17069 also
synthesized sophorolipids from sunflower oil cake reaching 0.48 g gds-1. It showed a more efficient
reduction in total cholesterol, low-density lipoprotein cholesterol, atherogenic index, liver
transaminase activity, malondialdehyde, and antioxidant enzymes than rosuvastatin in male albino
rats (Nooman et al., 2017).
Rhamnolipid (Fig. 4B) production by Pseudomonas aeruginosa attained a concentration of 6.25 µg ml-1
that was evaluated for its antiproliferative effects against human breast cancer cells (Varvaresou &
Iakovou, 2015). The highest reported rhamnolipid concentrations in SSF are 41.87 to 45.4 g L-1 of the
impregnating solution by Pseudomonas aeruginosa grown on a mixture of sugarcane bagasse and
sunflower seed meal and a mixture of sugarcane bagasse and corn bran, respectively (Camilios-Neto
et al., 2011; El-Housseiny et al., 2019).
The most studied lipopeptide biosurfactants are those produced by Bacillus strains, such as surfactin,
iturin, and fengycin (Varvaresou & Iakovou, 2015; Valdés-Velasco et al., 2022). They were produced
from millet by Bacillus subtilis SPB1 through SSF (20.8 mg gds-1), showing broad-spectrum
antimicrobial activity against microorganisms with a multidrug-resistant profile, such as
Staphylococcus aureus, Staphylococcus xylosus, Enterococcus faecalis, Klebsiella pneumonia, Escherichia coli,
and Candida albicans (Ghribi et al., 2012). Bacillus cereus SNAU01 generated lipopeptides using peanut
oil cake under SSF, which had potential application as an anti-biofilm agent against Pseudomonas
aeruginosa MTCC 2453 and Escherichia coli MTCC 2939 (Nalini et al., 2016). Surfactin (Fig. 4C) displays
activity against herpes viruses and retroviruses because it inhibits membrane fusion between the
virus and host cells, preventing the infection of epithelial cells (Varvaresou & Iakovou, 2015; Banat et
al., 2021). Surfactin exhibits anticancer activity against several cancer types, including breast, colon,
leukemia, hepatocellular, cervical, oral epidermoid, and pancreatic cancers (Wu et al., 2017). Bacillus
11
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
pumilus HY1 grown on soybeans as a solid support produced surfactin that inhibited the growth of
cancer cell lines MCF-7 and Caco-2 at 100 µg L-1 (Hong et al., 2021).
Iturin (Fig. 4D) has broad-spectrum antibacterial, hemolytic, anticarcinogenic, and thrombolytic
properties (Zhao et al., 2017; Wan et al., 2022). It was synthesized from soybean meal by Bacillus
velezensis ND under SSF, showing significant potential for industrial production (Shen et al., 2025).
Fig. 4 Chemical structures of biosurfactants produced by SSF. A) Lactonic sophorolipids. B) Rhamnolipid. C)
Surfactin. D) Iturin A.
Fig. 4 Estructuras químicas de biosurfactantes producidos por SSF: A) Sofrolípidos lactónicos. B) Ramnolípido.
C) Surfactina. D) Iturina A.
3.4 Polymers
Unlike small antimicrobial molecules, polymers offer an effective solution for surface-bound
pathogens, particularly when they are biocompatible and sustainable materials for medical
applications, such as prostheses and band aids. Furthermore, incorporating antibiotics into polymeric
matrices reduces their toxicity, enhances stability, and extends their half-life (Brooks & Brooks, 2014).
12
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Polymers are macromolecules formed from repeating units called monomers. They are an essential
class of molecules as they usually support the structural and biological functions of living organisms.
In addition to the biological activity studied, many other parameters can be used to characterize a
macromolecule, notably its monomeric composition and arrangement, chain length, and
morphology.
Moreover, for the same class of molecules, these parameters may have an essential influence on their
biological activity (Carboué et al., 2022). A distinction can be made regarding the inherent nature of
the antimicrobial properties, although this can also be applied to any biological activity. Indeed, some
polymers, such as natural polymers (e.g., chitosan) or synthetic polymers (e.g., polyethyleneimine),
exhibit inherent antimicrobial properties. In contrast, some polymers can be chemically
functionalized to obtain antimicrobial properties (Jain et al., 2014). It is also possible to functionalize
an existing antimicrobial polymer to improve its antimicrobial properties, as in the case where
phenolic acid derivatives were grafted onto chitosan (Wang et al., 2019). In the present section, the
focus is on the polymers produced by SSF; therefore, only natural polymers with inherent activities
were considered.
3.4.1 Carbohydrate polymers
Carbohydrate polymers or polysaccharides are the most prevalent biopolymers on Earth.
Among carbohydrate polymers, cellulose is the most abundant, followed by chitin (Shen et al., 2016).
A polymer is typically classified as a polysaccharide when it contains at least ten monosaccharide
units. Polysaccharides can be classified based on their composition (homo- and
heteropolysaccharides), type of glycosidic bonds, and cellular localization, within the cell wall,
secreted outside the cell as exopolysaccharides, or retained intracellularly as endopolysaccharides
(Osińska-Jaroszuk et al., 2015).
Most fungal exopolysaccharides are produced in SmF from Basidiomycetes and Ascomycetes.
Endophytic fungi are an excellent source of exopolysaccharides (Zeng, Yang, Wang, et al., 2019). For
instance, two heteropolysaccharides containing arabinose, glucose, mannose, and galactose were
produced by Fusarium solani grown on a solid medium containing rice, bean dregs, rice bran, and
corn bran for 30 days. However, due to the complexity of separating the medium from the mycelium
in SSF, it remains unclear whether these compounds are exopolysaccharides or endopolysaccharides.
Both molecules showed immunomodulatory activities, and one had interesting antioxidant potential
evaluated through a radical scavenging assay. This difference in antioxidant activity was attributed
to the difference in sugar composition between heteropolysaccharides. Indeed, a higher content of
galactose and glucose resulted in higher antioxidant activity (Zeng, et al., 2019a).
Nonetheless, bacterial exopolysaccharides may also be successfully produced using SSF. For instance,
Gram-negative Bacillus Kosakonia cowanii was cultivated on sugarcane bagasse and broadbean seed
capsules in SSF to produce exopolysaccharides. Considering the cost of the medium and comparing
their yield (41.62 mg gds-1) with the yield reported in the literature using SmF and similar conditions
(14.88 mg L-1), the authors suggested that 30 % cost saving could be obtained (Gao et al., 2020). SSF
media are not limited to lignocellulosic materials; for instance, squid processing byproducts in a
mixture with maize cob meal were successfully used as a solid medium to produce
exopolysaccharides from Bacillus licheniformis during the SSF process (Fang et al., 2013). Xanthan, a
heteropolysaccharide of high industrial importance for its use as a texturing agent in food, was
13
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
produced from Xanthomonas campestris grown on apple pomace, and the yields were comparable to
those obtained under SmF conditions (Stredansky & Conti, 1999). Moreover, it is worth mentioning
that the presence of oligosaccharides and phenolic compounds generated as degradation products
during the enzymatic degradation of lignocellulosic byproducts may also participate in the overall
antioxidant potential through inherent ant synergistic actions. Thus, when purification of the crude
extract is not required, the use of lignocellulosic byproducts in SSF may offer distinct advantages
(Forsan et al., 2025).
Another carbohydrate polymer is chitosan (Fig. 5A), which is an N-deacetylated chitin derivative.
This deacetylation process is typically incomplete; therefore, chitosan is a copolymer composed of N-
acetylglucosamine and glucosamine (Ravi Kumar, 2000). For chitosan, the degree of deacetylation
must be greater than 60 %. With a pKa value of 6.3, the amino groups confer solubility to chitosan in
mildly acidic aqueous solutions (Hamedi et al., 2018). In such solutions, these functional groups are
protonated, giving chitosan its polycationic properties and allowing its absorption onto negative
cellular membranes (Raafat et al., 2008). Several models have been proposed to explain the
mechanisms underlying the antimicrobial activity of chitosan; for instance, in gram-positive bacteria,
the peptidoglycans in the cell wall are hydrolyzed, generating a leakage of the intracellular
components and subsequent cellular death.
However, in gram-negative bacteria, chitosan interacts with lipoproteins and lipopolysaccharides
from the outer membrane, changing its permeability and blocking the transport of nutrients. Other
studies reported the antimicrobial intracellular action of chitosan, which, through crossing the cell
membrane, binds to DNA and prevents its transcription (Sahariah & Másson, 2017). Although the
antimicrobial activity of chitosan is influenced by its solubility, which is dependent on the degree of
deacetylation and solution pH, the role of molecular weight remains unclear and appears to vary
across microbial strains (Yilmaz Atay, 2019). Chitosan is traditionally produced by alkali extraction
of shells from molluscans and crustaceans. However, fungi also contain this macromolecule in their
cell wall. Thus, fungal chitosan can be produced using either SSF or SmF, circumventing the
additional steps involved in conventional production, such as decolorization and demineralization
(Ghormade et al., 2017). There are examples of the successful production of chitosan using SSF and
agroindustrial byproducts such as Rhizopus oryzae on soybean meal, corn straw, or potato peel
(Suntornsuk et al., 2002; Omogbai & Ikenebomeh, 2013; Kleekayai & Suntornsuk, 2011). The
difference in chitosan yields and properties may be observed between SSF and SmF for similar
nutritional conditions, but highly depends on the strain and medium used. Nwe et al. (2002), for
example, through using Gongronella butleri, observed that SmF led to 1.5-fold higher chitosan
production compared to the one obtained with SSF – the basis of comparison was the initial carbon
source –, although in this case, the chitosan had a lower molecular weight.
3.5 Poly(amino acids)
Poly(amino acids) are biocompatible and biodegradable polymers. A homopoly(amino acid)
is composed of one type of amino acid in its backbone. Although a wide variety of amino acids exists,
only four homopoly(amino acid)s have been reported in nature to date: poly(γ-glutamic acid), poly(ε-
L-lysine), poly(γ-L-diaminobutanoic acid), and poly(L-diaminopropionic acid). In contrast, polymers
consisting of more than one type of amino acid are called heteropoly(amino acid)s. For instance,
poly(L-arginyl-D-histidine) is produced by the ergot fungus Verticillium kibiense (Kurihara et al.,
14
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
2008). Poly(amino acid)s have interesting biological activities, primarily attributed to their poly-ionic
nature.
ε-Poly-lysine (Fig. 5B) is an oligomer consisting of 25–35 residues of L-lysine connected by unique
linkages between ε-amino groups and α-carboxyl groups. It is water-soluble, biodegradable, edible,
and non-toxic to humans and the environment (Shih et al., 2006). ε-Poly-lysine, similar to chitosan, is
a polycationic compound. Indeed, it has primary amine functions along its backbone and thus
displays cationic properties, with an isoelectric point of around pH = 9, facilitating electrostatic
interactions with negatively charged cell membranes, ultimately leading to membrane disruption
and cell death (Cai et al., 2025). The first study dealing with poly-ε-lysine production through SSF
reported a production yield of 86.62 mg gds-1 using Streptomyces albulus growing on a mixture of
rapeseed cake and wheat bran supplemented with glucose and (NH4)2SO4 incubated at 30 °C for 8
days (Xu et al., 2017). Notably, a comparable yield (75.51 mg gds-1) was also achieved under
composting conditions with 60 kg of the medium. Considering the cost of raw material and using a
yield of 25.8 g L-1 as a basis of comparison for production carried out in SmF, they concluded that SSF
would allow a 32 % reduction in the culture medium.
Some strains can simultaneously produce different homopoly(amino acid)s. A strain of S. albulus was
grown on spent mushroom residues using SSF to successfully produce ε-poly-lysine and poly(L-
diaminopropionic acid) (Fig. 5C) (Kurihara et al., 2008). This co-production is particularly promising
for the direct use of crude extracts given the complementary antimicrobial profiles of each compound.
For example, compared with ε-poly-lysine, poly(L-diaminopropionic acid) exhibits stronger
inhibitory activities against yeasts but weaker activities against bacteria (Xia et al., 2013).
Another noteworthy example is poly-γ-glutamic acid (Fig. 5D), which is extensively produced by
Bacillus species. It is an anionic homo-polyamide composed of D- and L-glutamic acid monomers
linked by an amide linkage between the α-amine and γ-carboxylic acid groups. Although anionic in
nature, poly-γ-glutamic acid displays notable antimicrobial activity, particularly against Gram-
positive bacteria. Both Gram-negative bacteria and poly-γ-glutamic acid are negatively charged, and
antimicrobial activity requires more product concentration. Moreover, this activity may be restricted
to ionic interactions and the hydrophobic nature of the molecule that participates in cell adhesion
(Ijadi Bajestani et al., 2018). Poly-γ-glutamic acid production was successfully performed using SSF
and a mixture of swine manure, soybean cake, and wheat bran as the culture medium (Chen et al.,
2005). Fang et al. (2020) used Bacillus amyloliquefaciens to produce poly-γ-glutamic acid by SSF on corn
stalks and soybean meal. The authors compared sterilized and non-sterilized solid media and
reported that although the yield was lower, the fermentation process was faster under non-sterilized
conditions. This finding is relevant from a process engineering standpoint, as sterilization steps
significantly increase production costs on an industrial scale.
15
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Fig. 5 Chemical structures of polymers produced by SSF. A) Chitosan. B) Poly-ε-lysine. C) Poly(L-
diaminopropionic acid). D) poly(γ-glutamic acid).
Fig. 5 Estructuras químicas de polímeros producidos por SSF. A) Quitosano. B) Poli-ε-lisina. C) Poli(ácido L-
diaminopropiónico). D) Poli(γ-ácido glutámico).
3.6 Enzymes
Some enzymes with pharmaceutical applications, such as amylases, lipases, and proteases,
have been developed under SSF. Amylases belong to a large group of glycosyl hydrolase enzymes
that catalyze the breakdown of complex carbohydrates such as starch and dextran. These enzymes
are used as diagnostic aids and show potential for diagnostic and therapeutic applications in cancer,
infection, wound healing, and drug delivery (Azzopardi et al., 2016). Stable amylases, active over a
broad range of pH and temperatures, have been produced from wheat bran as a solid substrate by
Bacillus amyloliquefaciens KCP2, Bacillus subtilis MTCC 121, and Gongronella butleri (Raul et al., 2014;
Prajapati et al., 2015; Cavalheiro et al., 2017).
Lipases, classified as triacylglycerol acyl hydrolases, are serine hydrolases that hydrolyze the ester
bonds of tri-, di-, and mono-glycerides to release fatty acids and glycerol. These enzymes are used to
synthesize pharmaceutical intermediates (Ramos Sanchez et al., 2015). For example, a lipase from
Geotrichum candidum was employed in the stereoselective acetylation of racemic [1- (hydroxy)-4-(3-
phenyl) butyl] phosphonic acid diethyl ester to produce a chiral intermediate for the chemical
synthesis of an anti-cholesterol drug (Ramos Sanchez et al., 2015). CAL-B lipase was used in a racemic
mixture of 2-pentanol to produce a chiral intermediate for the synthesis of anti-Alzheimer drugs
synthesis. Lipases from C. cylindracea and C. antartica were applied to resolve enantiomers of
flurbiprofen, naproxen, ibuprofen, suprofen, and baclofen, and to synthesize antiviral drugs such as
lobucavir, an antiviral of hepatitis B, and ribavirin (Ramos Sanchez et al., 2015). Lipases are mainly
produced by yeasts and filamentous fungi, which often exhibit higher lipase yields in SSF than in
SmF (Ramos Sanchez et al., 2015). Lipid-rich substrates, such as coconut oil cake, sesame oil cake,
babassu oil cake, olive cake, and palm kernel cake are preferred for lipase production (Ramos Sanchez
16
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
et al., 2015; Lopes et al., 2022). Yarrowia Lipolytica IMUFRJ50682, for instance, produced lipase with
hydrolytic activity under varying temperature and pH conditions in SSF using canola cake and
soybean meal (Souza et al., 2017). Similarly, rice bran and Jatropha seed cake were used for lipase
production by Aspergillus niger (Putri et al., 2020).
Proteases catalyze the hydrolysis of peptide bonds, breaking down proteins into smaller peptides or
amino acids (Steudler et al., 2019). Microbial alkaline serine proteases have notable pharmaceutical
relevance. Immobilized subtilisins have been incorporated into formulations for the treatment of
burns and wounds. Several protease therapies are currently under clinical investigation, owing to
their collagenase activity. Alkaline proteases have been used to treat conditions such as Dupuytren’s
disease, Peyronie’s disease, glaucoma, intervertebral disc herniation, debridement, keloids,
vitrectomy, and cellulite. Additionally, they are used in therapies for thrombolysis (urokinase,
fibrinolytic enzymes), hemophilia (factor VIIa), sepsis (activated protein C), muscle spasms
(botulinum toxin A and B), lymphocytic leukemia (asparaginase), purulent wounds, and abscesses
(elastoterase) (Matkawala et al., 2021). Neurospora crassa CGMCC3088 produced proteases via SSF
using okara as a substrate, showing extended stability in organic solvents, which is promising for
bioactive ingredient formulation (Zheng et al., 2020). Other commonly used solid substrates include
wheat straw, sugarcane bagasse, rice straw, and rice husks (Steudler et al., 2019).
Additionally, peptides with antioxidant activities can be produced using agro-industrial residues and
SSF. Bioactive peptides, derived from the hydrolysis of inactive parental proteins, have been shown
to reduce blood pressure and address complications associated with diabetes and cancer while also
exhibiting antioxidant properties (Manfredini et al., 2021). For instance, antioxidant peptides were
generated from grapeseed meal fermented by Bacillus subtilis 10160, with concentration-dependent-
activity (He et al., 2012). In another example, fermentation of soybean meal by B. amyloliquefaciens,
Lactobacillus sp., and Saccharomyces cerevisiae led to the elimination of trypsin inhibitors, synthesis of
proteases and small peptides, and an increase in phenolic compounds, ultimately enhancing
antioxidant activity (Manfredini et al., 2021).
3.7 Vitamins
Vitamins are organic compounds that are essential for the normal functioning of the body
because of their biochemical and biological roles. Since the body cannot synthesize some vitamins,
they must be obtained from the diet, with plants serving as their primary sources (Ball, 2004). Water-
soluble vitamins, such as riboflavin, nicotinic acid, nicotinamide, and vitamin B6 (Fig. 6A, B, C, D),
were produced through SSF of tempeh using Rhizopus oligosporus, R. arrhizus, and R. stolonifer.
Vitamin B12 (Fig. 6E) was synthesized when Citrobacter freundii and Klebsiella were added to the SSF
process (Pandey et al., 2000), highlighting the importance of microbial synergism. Furthermore,
Rhizopus oligosporus independently fermented both raw and roasted buckwheat groats, resulting from
1.5 to 3-fold increase in the concentrations of thiamine (B1), pyridoxin (B6), and L-ascorbic acid (Fig.
6F, 6H) (Wronkowska et al., 2015). Similarly, Saccharomyces cerevisiae, Candida utilis, and Torula utilis
enhanced vitamin C production from apple pomace powder (Joshi & Sandhu, 1996), whereas
Lactobacillus casei improved the vitamin B1 and B2 content of soybean flour (Li et al., 2020).
17
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Fig. 6 Chemical structures of vitamins produced by SSF. A) Riboflavin. B) Nicotinic acid. C) Nicotinamide. D)
Vitamin B6. E) Vitamin B12. F) Vitamin B1. H) L-Ascorbic acid.
Fig. 6 Estructuras químicas de vitaminas producidas por SSF. A) Riboflavina. B) Ácido nicotínico. C)
Nicotinamida. D) Vitamina B6. E) Vitamina B12. F) Vitamina B1. H) Ácido L-ascórbico.
3.8 Miscellaneous
Some secondary metabolites in pharmaceutical products, such as carotenoids, lovastatin, and
cordycepin, show great promise owing to their therapeutic properties. Carotenoids, such as lycopene,
exhibit potent antioxidant activity and have been associated with improvements in cardiovascular
diseases, inflammatory events, oxidative stress-mediated dysfunction, and cancer resistance.
Lycopene was extracted through SSF of tomatoe waste using Aspergillus niger GH1. It was found that
total carotenoid recovery was below 70 % at moisture, highlighting the importance of this parameter
in the bioprocess (Mendez-Carmona et al., 2022). Lovastatin (Fig. 7A), a widely used
hypercholesterolemic drug, was efficiently produced via SSF of wheat bran by Aspergillus terreus
ATCC 10020, reaching a yield of 8.67 mg gds-1. In this way, lovastatin significantly reduced insulin
levels, body mass, LDL-C, triglycerides, blood glucose, and thiobarbituric acid-reactive substances in
mice fed a high-fat diet (Al-Saman et al., 2021). Cordycepin (Fig. 7B), a nucleoside derivative
synthesized by Cordyceps militaris, is commonly used as a functional food and medicine in Southeast
Asia to treat and prevent obesity. It also exhibits anticancer, antiviral, antileukemic, and
hypolipidemic activities. SSF using brown rice has emerged as a promising method for cordycepin
production, as it is more difficult and costly to purify through chemical synthesis than through
biological pathways (Wen et al., 2014).
18
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Fig. 7 Chemical structures of miscellaneous secondary metabolites produced by SSF. A) Lovastatin. B)
Cordycepin.
Fig. 7 Estructuras químicas de metabolitos secundarios diversos producidos por SSF. A) Lovastatina.
B) Cordicepina.
Table 2. Microorganisms and residues used to produce bioactive compounds by Solid-state fermentation.
Tabla 2. Microorganismos y residuos utilizados en la producción de compuestos bioactivos mediante
fermentación en estado sólido.
Compound
Bioactive
compound
Microorganism
Solid residue / substrate
Reference
Antibiotics
Cephalosporin C
Acremonium chrysogenum
Sugarcane bagasse
Tabaraie et al., 2012
Rifamycin B
Amycolatopsis mediterranei
Nut shells, coconut oil cake
Vastrad &
Neelagund, 2012
Paromomycin
Streptomyces rimosus
Corn bran
El-Housseiny et al.,
2021
Aroma
compounds
Vanillin
Enterobacter hormaechei
Sugarcane bagasse, fruit peels
Mehmood et al.,
2022
2-Phenylethanol
Pichia kudriavzevii
Apple pomace, sugarcane
bagasse
Martínez-Ávila et
al., 2020
Biosurfactants
Sophorolipids
Candida bombicola
Sunflower oil cake + soybean oil
Rashad et al., 2014
Rhamnolipids
Pseudomonas aeruginosa
Sugarcane bagasse + corn bran
Camilios-Neto et
al., 2011
Surfactin
Bacillus subtilis
Millet, peanut oil cake
Ghribi et al., 2012
Polymers
Chitosan
Rhizopus oryzae
Potato peel
Kleekayai &
Suntornsuk, 2011
ε-Poly-L-lysine
Streptomyces albulus
Rapeseed cake + wheat bran
Xu et al., 2017
Enzymes
Amylases
Bacillus amyloliquefaciens
Wheat bran
Prajapati et al.,
2015
Lipases
Yarrowia lipolytica
Canola cake, soybean meal
Souza et al., 2017
Others
Riboflavin, niacin
Rhizopus oligosporus
Soybeans (tempeh)
Pandey et al., 2000
Lovastatin
Aspergillus terreus
Wheat bran
Al-Saman et al.,
2021
Cordycepin
Cordyceps militaris
Brown rice
Wen et al., 2014
19
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
4. Future perspectives of Solid-state fermentation
Although solid-state fermentation (SSF) offers significant advantages to produce bioactive
compounds with pharmaceutical potential, several technical and regulatory limitations still
constrain its large-scale implementation. The inherent heterogeneity of SSF systems complicates
accurate process monitoring and control, particularly for critical parameters such as temperature,
moisture content, pH, and oxygen availability. The integration of advanced sensing technologies,
predictive modeling, and data-driven control strategies represents a promising pathway to improve
process robustness, reproducibility, and scalability.
In addition, the variability of solid substrates, together with the absence of dedicated regulatory
frameworks for SSF-based pharmaceutical processes, remains a major barrier to industrial adoption.
Future progress will rely on substrate standardization, microbial strain improvement, bioreactor
desing, and the establishment of clear regulatory guidelines, enabling SSF to evolve from a
predominantly laboratory-scale approach into a reliable, scalable, and sustainable platform for
pharmaceutical bioprocesses.
5. Conclusion
Pharmaceutical products that contain microbial bioactive compounds play a vital role in
promoting human health and represent promising alternatives to synthetic drugs and health care
products, offering greater selectivity, reduced toxicity, and fewer side effects. Therefore, the
development of novel fermentation strategies to enhance production is important. SSF is a
sustainable and cost-effective approach for the pharmaceutical industry, offering high product
yields while utilizing low-cost substrates and minimizing environmental impact. Pharmaceutical
products typically require high purity, and SSF often uses agro-industrial byproducts. Therefore, the
resulting crude extracts tend to be complex and may require extensive downstream processing to
meet purity standards. These additional purification steps can significantly increase the overall
production costs. Finally, most current studies on SSF for bioactive compound production are
limited to lab-scale bioreactors. Therefore, further studies are necessary to address the challenges
related to the process scale-up and control. By addressing current limitations and showcasing
innovative applications, solid-state fermentation is positioned as a viable complementary strategy
for pharmaceutical bioprocesses.
Author contributions
L. M. V. V.: Conceptualización, redacción-revisión y edición. Q. C.: Conceptualización,
redacción-revisión. S. H. O.: Supervisión, redacción – revisión. E. F. T.: Supervisión, redacción –
revisión y edición. I. N. C. S.: Conceptualización, redacción-revisión y edición.
20
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Acknowledgements
We are grateful to all our laboratory colleagues and research personnel for their helpful
advice and assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
References
Al-Saman, M. A., Helmy, M. A., Abdella, A., Wilkins, M. R., El Khalik Gobba, N. A., & Mahrous, H.
(2021). Optimization of lovastatin production by Aspergillus terreus ATCC 10020 using solid-
state fermentation and its pharmacological applications. Biocatalysis and Agricultural
Biotechnology, 31, 101906. https://doi.org/10.1016/J.BCAB.2021.101906
Arya, S. S., Rookes, J. E., Cahill, D. M., & Lenka, S. K. (2021). Vanillin: a review on the therapeutic
prospects of a popular flavouring molecule. Advances in Traditional Medicine, 21, 1–17.
https://doi.org/10.1007/s13596-020-00531-w
Azzopardi, E., Lloyd, C., Teixeira, S. R., Conlan, R. S., & Whitaker, I. S. (2016). Clinical applications
of amylase: Novel perspectives. Surgery, 160(1), 26–37.
https://doi.org/10.1016/J.SURG.2016.01.005
Ball, G.F.M. (2004). Nutritional Aspects of Vitamins. In: Ball, G. F. M. (ed.) Vitamins: Their Role in the
Human Body (p. 8). John Wiley & Sons.
Banat, I. M., Carboué, Q., Saucedo-Castañeda, G., & de Jesús Cázares-Marinero, J. (2021).
Biosurfactants: The green generation of speciality chemicals and potential production using
Solid-State fermentation (SSF) technology. Bioresource Technology, 320 (Part A), 124222.
https://doi.org/10.1016/J.BIORTECH.2020.124222
Brekke, K. R., Dalen, D. M., & Straume, O. R. (2025). Taking the Competitor’s Pill: When Combination
Therapies Enter Pharmaceutical Markets. Journal of Health Economics, 101: 102976.
https://doi.org/10.1016/j.jhealeco.2025.102976
Brooks, D. B., & Brooks, A. E. (2014). Therapeutic strategies to combat antibiotic resistance. Advanced
Drug Delivery Reviews, 78, 14–27. https://doi.org/10.1016/j.addr.2014.10.027
Cai, J.-Y., Zhang, C.-J., Wang, J.-Q. Liao, A.-M., Hui, M., Pan, L., & Chen, X.-S. (2025). Advances in ε-
Poly-Lysine Biosynthesis, Selection of High-Yielding Strains and Regulatory Mechanisms.
Biotechnology Journal, 20(9), e70111. https://doi.org/10.1002/biot.70111
Camilios-Neto, D., Bugay, C., de Santana-Filho, A. P., Joslin, T., de Souza, L. M., Sassaki, G. L.,
Mitchell, D. A., & Krieger, N. (2011). Production of rhamnolipids in solid-state cultivation
using a mixture of sugarcane bagasse and corn bran supplemented with glycerol and
soybean oil. Applied Microbiology and Biotechnology, 89, 1395–1403.
https://doi.org/10.1007/s00253-010-2987-3
Carboué, Q., Fadlallah, S., Lopez, M., & Allais, F. (2022). Progress in Degradation Behavior of Most
Common Types of Functionalized Polymers: A Review. Macromolecular Rapid
Communications, 43(13), 2200254. https://doi.org/10.1002/marc.202200254
21
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Cavalheiro, G. F., Sanguine, I. S., Santos, F. R. D. S., Da Costa, A. C., Fernandes, M., da Paz, M. F.,
Fonseca, G. G., & Leite, R. S. R. (2017). Catalytic Properties of Amylolytic Enzymes Produced
by Gongronella butleri Using Agroindustrial Residues on Solid-State Fermentation. BioMed
Research International, 2017, 507523. https://doi.org/10.1155/2017/7507523
Chen, C., Li, D., Li, R., Shen, F., Xiao, G., & Zhou, J. (2021). Enhanced biosurfactant production in a
continuous fermentation coupled with in situ foam separation. Chemical Engineering and
Processing - Process Intensification, 159, 108206. https://doi.org/10.1016/J.CEP.2020.108206
Chen, X., Chen, S., Sun, M., & Yu, Z. (2005). High yield of poly-γ-glutamic acid from Bacillus subtilis
by solid-state fermentation using swine manure as the basis of a solid substrate. Bioresource
Technology, 96(17), 1872–1879. https://doi.org/10.1016/j.biortech.2005.01.033
Chilakamarry, C. R., Mimi Sakinah, A. M. M., Zularisam, A. W., Sirohi, R., Khilji, I. A., Ahmad, N.,
& Pandey, A. (2022). Advances in solid-state fermentation for bioconversion of agricultural
wastes to value-added products: Opportunities and challenges. Bioresource Technology, 343,
126065. https://doi.org/10.1016/j.biortech.2021.126065
Cordero-Soto, I. N., Castillo-Araiza, C. O., García-Martínez, L. E., Prado-Barragán, A., & Huerta-
Ochoa, S. (2020). Solid/gas biocatalysis for aroma production: An alternative process of white
biotechnology. Biochemical Engineering Journal, 164, 107767.
https://doi.org/10.1016/j.bej.2020.107767
Cordero-Soto, I.N., Contreras-Hernández, M.G., Palmerín-Carreño, D.M., Nuñez-García, I.C., &
Rutiaga-Quiñones, O.M. (2025). Microbial-Based Technologies for the Reuse of Food By-
Products. In: Aguilar-Zárate, P., Haghi, A. K., & Gámez-García, R. (eds.). Reducing Food Loss
and Waste. (pp.121–144). Springer, Cham. https://doi.org/10.1007/978-3-031-91693-9_6
Costa, R. dos S., de Almeida, S. S., Cavalcanti, E. d’A. C., Freire, D. M. G., Moura-Nunes, N.,
Monteiro, M., & Perrone, D. (2021). Enzymes produced by solid state fermentation of agro-
industrial by-products release ferulic acid in bioprocessed whole-wheat breads. Food
Research International, 140, 109843. https://doi.org/10.1016/j.foodres.2020.109843
De la Cruz-Quiroz, R., Ascacio-Valdés, J. A., Rodríguez-Herrera, R., Roussos, S., & Aguilar, C. N.
(2019). Phytopathogen Biomass as Inducer of Antifungal Compounds by Trichoderma
asperellum Under Solid-State Fermentation. In: Singh, H., Keswani, C., Reddy, M.,
Sansinenea, E., García-Estrada, C. (eds) Secondary Metabolites of Plant Growth Promoting
Rhizomicroorganisms. (pp. 113–124). Springer Singapore. https://doi.org/10.1007/978-981-13-
5862-3_6
Dolman, B. M., Wang, F., & Winterburn, J. B. (2019). Integrated production and separation of
biosurfactants. Process Biochemistry, 83, 1–8. https://doi.org/10.1016/j.procbio.2019.05.002
El-Housseiny, G. S., Aboshanab, K. M., Aboulwafa, M. M., & Hassouna, N. A. (2019). Rhamnolipid
production by a gamma ray-induced Pseudomonas aeruginosa mutant under solid state
fermentation. AMB Express, 9, 7. https://doi.org/10.1186/s13568-018-0732-y
El-Housseiny, G. S., Ibrahim, A. A., Yassien, M. A., & Aboshanab, K. M. (2021). Production and
statistical optimization of Paromomycin by Streptomyces rimosus NRRL 2455 in solid state
fermentation. BMC Microbiology, 21, 34. https://doi.org/10.1186/s12866-021-02093-6
Fang, J., Liu, Y., Huan, C., Xu, L., Ji, G., & Yan, Z. (2020). Comparison of poly-γ-glutamic acid
production between sterilized and non-sterilized solid-state fermentation using agricultural
waste as substrates. Journal of Cleaner Production, 255, 120248.
https://doi.org/10.1016/j.jclepro.2020.120248
Fang, Y., Ahmed, S., Liu, S., Wang, S., Lu, M., & Jiao, Y. (2013). Optimization of antioxidant
exopolysaccharidess production by Bacillus licheniformis in solid state fermentation.
Carbohydrate Polymers, 98(2), 1377–1382. https://doi.org/10.1016/j.carbpol.2013.07.076
22
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Fent, K., Weston, A. A., & Caminada, D. (2006). Ecotoxicology of human pharmaceuticals. Aquatic
Toxicology, 76(2), 122–159. https://doi.org/10.1016/J.AQUATOX.2005.09.009
Finkler, A. T. J., Biz, A., Pitol, L. O., Medina, B. S., Luithardt, H., Luz, L. F. de L., Krieger, N., &
Mitchell, D. A. (2017). Intermittent agitation contributes to uniformity across the bed during
pectinase production by Aspergillus niger grown in solid-state fermentation in a pilot-scale
packed-bed bioreactor. Biochemical Engineering Journal, 121, 1–12.
https://doi.org/10.1016/j.bej.2017.01.011
Finkler, A. T. J., Weber, M. Z., Fuchs, G. A., Scholz, L. A., de Lima L. Jr, L. F., Krieger, N., Mitchell,
D. A., & Jorge, L. M. de M. (2021). Estimation of heat and mass transfer coefficients in a pilot
packed-bed solid-state fermentation bioreactor. Chemical Engineering Journal, 408, 127246.
https://doi.org/10.1016/j.cej.2020.127246
Forsan, C. F., Marin, D. F. C., & Brienzo, M. (2025). Revealing Antioxidant Activity of
Cellooligosaccharides and Xylooligosaccharides from Banana Leaves, Pseudostem and
Guava Seed Cake. AppliedChem, 5(3), 21. https://doi.org/10.3390/appliedchem5030021
Gao, H., Lu, C., Wang, H., Wang, L., Yang, Y., Jiang, T., Li, S., Xu, D., & Wu, L. (2020). Production
exopolysaccharide from Kosakonia cowanii LT-1 through solid-state fermentation and its
application as a plant growth promoter. International Journal of Biological Macromolecules, 150,
955–964. https://doi.org/10.1016/j.ijbiomac.2019.10.209
Ghormade, V., Pathan, E. K., & Deshpande, M. V. (2017). Can fungi compete with marine sources
for chitosan production? International Journal of Biological Macromolecules, 104 (Part B), 1415–
1421. https://doi.org/10.1016/j.ijbiomac.2017.01.112
Ghribi, D., Abdelkefi-Mesrati, L., Mnif, I., Kammoun, R., Ayadi, I., Saadaoui, I., Maktouf, S., &
Chaabouni-Ellouze, S. (2012). Investigation of Antimicrobial Activity and Statistical
Optimization of Bacillus subtilis SPB1 Biosurfactant Production in Solid-State Fermentation.
Journal of Biomedicine and Biotechnology, 2012, 373682. https://doi.org/10.1155/2012/373682
Gong, Z., He, Q., Che, C., Liu, J., & Yang, G. (2020). Optimization and scale-up of the production of
rhamnolipid by Pseudomonas aeruginosa in solid-state fermentation using high-density
polyurethane foam as an inert support. Bioprocess and Biosystems Engineering, 43(3), 385–392.
https://doi.org/10.1007/s00449-019-02234-2
Hadj Saadoun, J., Bertani, G., Levante, A., Vezzosi, F., Ricci, A., Bernini, V., & Lazzi, C. (2021).
Fermentation of Agri-Food Waste: A Promising Route for the Production of Aroma
Compounds. Foods, 10(4), 707. https://doi.org/10.3390/foods10040707
Hamedi, H., Moradi, S., Hudson, S. M., & Tonelli, A. E. (2018). Chitosan based hydrogels and their
applications for drug delivery in wound dressings: A review. Carbohydrate Polymers, 199,
445–460. https://doi.org/10.1016/j.carbpol.2018.06.114
He, R., Ju, X., Yuan, J., Wang, L., Girgih, A. T., & Aluko, R. E. (2012). Antioxidant activities of
rapeseed peptides produced by solid state fermentation. Food Research International, 49(1),
432–438. https://doi.org/10.1016/J.FOODRES.2012.08.023
Hong, S.-Y., Lee, D.-H., Lee, J.-H., Haque, M. A., & Cho, K.-M. (2021). Five Surfactin Isomers
Produced during Cheonggukjang Fermentation by Bacillus pumilus HY1 and Their
Properties. Molecules, 26(15), 4478. https://doi.org/10.3390/molecules26154478
Ijadi Bajestani, M., Mousavi, S. M., Mousavi, S. B., Jafari, A., & Shojaosadati, S. A. (2018). Purification
of extra cellular poly-γ-glutamic acid as an antibacterial agent using anion exchange
chromatography. International Journal of Biological Macromolecules, 113, 142–149.
https://doi.org/10.1016/j.ijbiomac.2018.02.082
Inoue, M., Sumii, Y., & Shibata, N. (2020). Contribution of Organofluorine Compounds to
Pharmaceuticals. ACS Omega, 5(19), 10633–10640. https://doi.org/10.1021/acsomega.0c00830
23
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Jain, A., Duvvuri, L. S., Farah, S., Beyth, N., Domb, A. J., & Khan, W. (2014). Antimicrobial Polymers.
Advanced Healthcare Materials, 3(12), 1969–1985. https://doi.org/10.1002/adhm.201400418
Jiménez-Peñalver, P., Rodríguez, A., Daverey, A., Font, X., & Gea, T. (2019). Use of wastes for
sophorolipids production as a transition to circular economy: state of the art and
perspectives. Reviews in Environmental Science and Bio/Technology, 18(3), 413–435.
https://doi.org/10.1007/s11157-019-09502-3
Joshi, V. K., & Sandhu, D. K. (1996). Preparation and evaluation of an animal feed byproduct
produced by solid-state fermentation of apple pomace. Bioresource Technology, 56(2–3), 251–
255. https://doi.org/10.1016/0960-8524(96)00040-5
Kagliwal, L. D., Survase, S. A., & Singhal, R. S. (2009). A novel medium for the production of
cephamycin C by Nocardia lactamdurans using solid-state fermentation. Bioresource
Technology, 100(9), 2600–2606. https://doi.org/10.1016/j.biortech.2008.11.046
Kardos, N., & Demain, A. L. (2011). Penicillin: the medicine with the greatest impact on therapeutic
outcomes. Applied Microbiology and Biotechnology, 92(4), 677–687.
https://doi.org/10.1007/s00253-011-3587-6
Kleekayai, T., & Suntornsuk, W. (2011). Production and characterization of chitosan obtained from
Rhizopus oryzae grown on potato chip processing waste. World Journal of Microbiology and
Biotechnology, 27(5), 1145–1154. https://doi.org/10.1007/s11274-010-0561-x
Krishania, M., Sindhu, R., Binod, P., Ahluwalia, V., Kumar, V., Sangwan, R. S., & Pandey, A. (2018).
Chapter 5-Design of Bioreactors in Solid-State Fermentation. In: Pandey, A., Larroche, C., &
Soccol, C. R. (eds.). Current Developments in Biotechnology and Bioengineering (pp. 83–96).
Elsevier. https://doi.org/10.1016/B978-0-444-63990-5.00005-0
Kumar, V., Ahluwalia, V., Saran, S., Kumar, J., Patel, A. K., & Singhania, R. R. (2021). Recent
developments on solid-state fermentation for production of microbial secondary
metabolites: Challenges and solutions. Bioresource Technology, 323, 124566.
https://doi.org/10.1016/j.biortech.2020.124566
Kurihara, I., Ishii, Y., Kirimura, K., & Kino, K. (2008). Enhancement of poly(arginyl-histidine)
production by Verticillium kibiense E18. Biochemical Engineering Journal, 42(3), 270–275.
https://doi.org/10.1016/j.bej.2008.07.007
Li, S., Jin, Z., Hu, D., Yang, W., Yan, Y., Nie, X., Lin, J., Zhang, Q., Gai, D., Ji, Y., & Chen, X. (2020).
Effect of solid-state fermentation with Lactobacillus casei on the nutritional value, isoflavones,
phenolic acids and antioxidant activity of whole soybean flour. LWT, 125, 109264.
https://doi.org/10.1016/j.lwt.2020.109264
Lopes, M., Miranda, S. M., Costa, A. R., Pereira, A. S., & Belo, I. (2022). Yarrowia lipolytica as a
biorefinery platform for effluents and solid wastes valorization – challenges and
opportunities. Critical Reviews in Biotechnology, 42(2), 163–183.
https://doi.org/10.1080/07388551.2021.1931016
Ma, Y. C., Huang, P., Wang, X. L., & Liu, G. Q. (2023). Multi-omics analysis unravels positive effect
of rotenone on the cordycepin biosynthesis in submerged fermentation of Cordyceps militaris.
Bioresource Technology, 373, 128705. https://doi.org/10.1016/J.BIORTECH.2023.128705
Mahanta, N., Gupta, A., & Khare, S. K. (2008). Production of protease and lipase by solvent tolerant
Pseudomonas aeruginosa PseA in solid-state fermentation using Jatropha curcas seed cake as
substrate. Bioresource Technology, 99(6), 1729–1735.
https://doi.org/10.1016/j.biortech.2007.03.046
Małgorzata, W., Joanna, H., & Mariusz Konrad, P. (2015). Effect of solid-state fermentation with
Rhizopus oligosporus on bioactive compounds and antioxidant capacity of raw and roasted
24
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
buckwheat groats. Italian Journal of Food Science, 27(4), 424-431. https://doi.org/10.14674/1120-
1770/ijfs.v373
Manfredini, P. G., Cavanhi, V. A. F., Costa, J. A. V., & Colla, L. M. (2021). Bioactive peptides and
proteases: characteristics, applications and the simultaneous production in solid-state
fermentation. Biocatalysis and Biotransformation, 39(5), 360–377.
https://doi.org/10.1080/10242422.2020.1849151
Mantzouridou, F. T., Paraskevopoulou, A., & Lalou, S. (2015). Yeast flavour production by solid state
fermentation of orange peel waste. Biochemical Engineering Journal, 101, 1–8.
https://doi.org/10.1016/J.BEJ.2015.04.013
Martău, G. A., Călinoiu, L.-F., & Vodnar, D. C. (2021). Bio-vanillin: Towards a sustainable industrial
production. Trends in Food Science & Technology, 109, 579–592.
https://doi.org/10.1016/j.tifs.2021.01.059
Martínez-Avila, O., Muñoz-Torrero, P., Sánchez, A., Font, X., & Barrena, R. (2021). Valorization of
agro-industrial wastes by producing 2-phenylethanol via solid-state fermentation: Influence
of substrate selection on the process. Waste Management, 121, 403–411.
https://doi.org/10.1016/j.wasman.2020.12.036
Martínez-Avila, O., Sánchez, A., Font, X., & Barrena, R. (2020). 2-phenylethanol (rose aroma)
production potential of an isolated Pichia kudriavzevii through solid-state fermentation.
Process Biochemistry, 93, 94–103. https://doi.org/10.1016/j.procbio.2020.03.023
Martínez, O., Sánchez, A., Font, X., & Barrena, R. (2018). Bioproduction of 2-phenylethanol and 2-
phenethyl acetate by Kluyveromyces marxianus through the solid-state fermentation of
sugarcane bagasse. Applied Microbiology and Biotechnology, 102(11), 4703–4716.
https://doi.org/10.1007/s00253-018-8964-y
Matkawala, F., Nighojkar, S., Kumar, A., & Nighojkar, A. (2021). Microbial alkaline serine proteases:
Production, properties and applications. World Journal of Microbiology and Biotechnology,
37(4), 63. https://doi.org/10.1007/s11274-021-03036-z
Mehmood, T., Ahmed, S., Waseem, R., Saeed, S., Ahmed, W., Irfan, M., & Ullah, A. (2022).
Valorization of Fruit Peels into Biovanillin and Statistical Optimization of Process Using
Enterobacter hormaechei through Solid-State Fermentation. Fermentation, 8(2), 40.
https://doi.org/10.3390/fermentation8020040
Mehmood, T., Saleem, F., Javed, S., Nawaz, S., Sultan, A., Safdar, A., Ullah, A., Waseem, R., Saeed,
S., Abbas, M., Bilal, M., Ahmad, M. M., & Firyal, S. (2022). Biotransformation of Agricultural
By-Products into Biovanillin through Solid-State Fermentation (SSF) and Optimization of
Different Parameters Using Response Surface Methodology (RSM). Fermentation, 8(5), 206.
https://doi.org/10.3390/fermentation8050206
Mendez-Carmona, J. Y., Ramírez-Guzman, K. N., Ascacio-Valdes, J. A., Sepulveda, L., & Aguilar, C.
N. (2022). Solid-state fermentation for recovery of carotenoids from tomato waste. Innovative
Food Science & Emerging Technologies, 80, 103108. https://doi.org/10.1016/j.ifset.2022.103108
Mierzejewska, J., Dąbkowska, K., Chreptowicz, K., & Sokołowska, A. (2019). Hydrolyzed corn stover
as a promising feedstock for 2-phenylethanol production by nonconventional yeast. Journal
of Chemical Technology & Biotechnology, 94(3), 777–784. https://doi.org/10.1002/jctb.5823
Mizumoto, S., Hirai, M., & Shoda, M. (2006). Production of lipopeptide antibiotic iturin A using
soybean curd residue cultivated with Bacillus subtilis in solid-state fermentation. Applied
Microbiology and Biotechnology, 72(5), 869–875. https://doi.org/10.1007/s00253-006-0389-3
Nalini, S., Parthasarathi, R., & Prabudoss, V. (2016). Production and characterization of lipopeptide
from Bacillus cereus SNAU01 under solid state fermentation and its potential application as
25
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
anti-biofilm agent. Biocatalysis and Agricultural Biotechnology, 5, 123–132.
https://doi.org/10.1016/j.bcab.2016.01.007
Nooman, M. U., Mahmoud, M. H., Al-kashef, A. S., & Rashad, M. M. (2017). Hypocholesterolemic
impact of newly isolated sophorolipids produced by microbial conversion of safflower oil
cake in rats fed high-fat and cholesterol diet. Grasas y Aceites, 68(3), e212.
https://doi.org/10.3989/gya.0219171
Nwe, N., Chandrkrachang, S., Stevens, W. F., Maw, T., Tan, T. K., Khor, E., & Wong, S. M. (2002).
Production of fungal chitosan by solid state and submerged fermentation. Carbohydrate
Polymers, 49(2), 235–237. https://doi.org/10.1016/S0144-8617(01)00355-1
Oiza, N., Moral-Vico, J., Sánchez, A., Oviedo, E. R., & Gea, T. (2022). Solid-State Fermentation from
Organic Wastes: A New Generation of Bioproducts. Processes, 10(12), 2675.
https://doi.org/10.3390/pr10122675
Omogbai, B., & Ikenebomeh, M. (2013). Solid-state fermentative production and bioactivity of fungal
chitosan. Journal of Microbiology, Biotechnology and Food Sciences, 3(2), 172–175.
https://office2.jmbfs.org/index.php/JMBFS/article/view/7063
Osińska-Jaroszuk, M., Jarosz-Wilkołazka, A., Jaroszuk-Ściseł, J., Szałapata, K., Nowak, A., Jaszek, M.,
Ozimek, E., & Majewska, M. (2015). Extracellular polysaccharides from Ascomycota and
Basidiomycota: production conditions, biochemical characteristics, and biological
properties. World Journal of Microbiology and Biotechnology, 31(12), 1823–1844.
https://doi.org/10.1007/s11274-015-1937-8
Pandey, A. (2003). Solid-state fermentation. Biochemical Engineering Journal, 13(2-3), 81–84.
https://doi.org/10.1016/S1369-703X(02)00121-3
Pandey, A., Soccol, C. R., & Mitchell, D. (2000). New developments in solid state fermentation: I-
bioprocesses and products. Process Biochemistry, 35(10), 1153–1169.
https://doi.org/10.1016/S0032-9592(00)00152-7
Paul, V., Rai, D. C., T.S, R. L., Srivastava, S. K., & Tripathi, A. D. (2021). A comprehensive review on
vanillin: its microbial synthesis, isolation and recovery. Food Biotechnology, 35(1), 22–49.
https://doi.org/10.1080/08905436.2020.1869039
Perez, C. L., Casciatori, F. P., & Thoméo, J. C. (2019). Strategies for scaling-up packed-bed bioreactors
for solid-state fermentation: The case of cellulolytic enzymes production by a thermophilic
fungus. Chemical Engineering Journal, 361, 1142–1151. https://doi.org/10.1016/j.cej.2018.12.169
Prajapati, V. S., Trivedi, U. B., & Patel, K. C. (2015). A statistical approach for the production of
thermostable and alklophilic alpha-amylase from Bacillus amyloliquefaciens KCP2 under
solid-state fermentation. 3 Biotech, 5(2), 211–220. https://doi.org/10.1007/s13205-014-0213-1
Putri, D. N., Khootama, A., Perdani, M. S., Utami, T. S., & Hermansyah, H. (2020). Optimization of
Aspergillus niger lipase production by solid state fermentation of agro-industrial waste.
Energy Reports, 6(Supplement 1), 331–335. https://doi.org/10.1016/J.EGYR.2019.08.064
Raafat, D., von Bargen, K., Haas, A., & Sahl, H.-G. (2008). Insights into the Mode of Action of
Chitosan as an Antibacterial Compound. Applied and Environmental Microbiology, 74(12),
3764–3773. https://doi.org/10.1128/AEM.00453-08
Ramos Sánchez, L. B., Cujilema-Quitio, M. C., Julian-Ricardo, M. C., Cordova, J., & Fickers, P. (2015).
Fungal Lipase Production by Solid-State Fermentation. Journal of Bioprocessing &
Biotechniques, 05(02), 1000203. https://www.hilarispublisher.com/open-access/fungal-lipase-
production-by-solidstate-fermentation-2155-9821.1000203.pdf
Rashad, M. M., Nooman, M. U., Ali, M. M., Al-kashef, A. S., & Mahmoud, A. E. (2014). Production,
characterization and anticancer activity of Candida bombicola sophorolipids by means of solid
26
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
state fermentation of sunflower oil cake and soybean oil. Grasas y Aceites, 65(2), e017.
https://doi.org/10.3989/gya.098413
Raul, D., Biswas, T., Mukhopadhyay, S., Kumar Das, S., & Gupta, S. (2014). Production and partial
purification of alpha amylase from Bacillus subtilis (mtcc 121) using solid state fermentation.
Biochemistry Research International, 2014, 68141. https://doi.org/10.1155/2014/568141
Ravi Kumar, M. N. V. (2000). A review of chitin and chitosan applications. Reactive and Functional
Polymers, 46(1), 1–27. https://doi.org/10.1016/S1381-5148(00)00038-9
Raza, Z. A., Shahzad, Q., Rehman, A., Taqi, M., & Ayub, A. (2022). Biosurfactants in the sustainable
eradication of SARS COV-2 from the environmental surfaces. 3 Biotech, 12(10), 273.
https://doi.org/10.1007/s13205-022-03320-1
Ribeiro, B. G., Guerra, J. M. C., & Sarubbo, L. A. (2020). Biosurfactants: Production and application
prospects in the food industry. Biotechnology Progress, 36(5), e3030.
https://doi.org/10.1002/btpr.3030
Robinson, T., & Nigam, P. (2003). Bioreactor design for protein enrichment of agricultural residues
by solid state fermentation. Biochemical Engineering Journal, 13(2–3), 197–203.
https://doi.org/10.1016/S1369-703X(02)00132-8
Salehi, M., & Rashidinejad, A. (2025). Multifaceted Roles of Plant-Derived Bioactive Polysaccharides:
A Review of Their Biological Functions, Delivery, Bioavailability, and Applications within
the Food and Pharmaceutical Sectors. International Journal of Biological Macromolecules 290,
138855. https://doi.org/10.1016/j.ijbiomac.2024.138855
Sahariah, P., & Másson, M. (2017). Antimicrobial Chitosan and Chitosan Derivatives: A Review of
the Structure–Activity Relationship. Biomacromolecules, 18(11), 3846–3868.
https://doi.org/10.1021/acs.biomac.7b01058
Shen, X., Shamshina, J. L., Berton, P., Gurau, G., & Rogers, R. D. (2016). Hydrogels based on cellulose
and chitin: fabrication, properties, and applications. Green Chemistry, 18(1), 53–75.
https://doi.org/10.1039/C5GC02396C
Shen, Y., Cao, X., Tang, Z. 2025. Simultaneous Production of MK-7 and Iturin A by Bacillus velezensis
ND. Applied Biochemistry and Biotechnology, 197, 268–287. https://doi.org/10.1007/s12010-
024-05012-3
Shih, I.-L., Shen, M.-H., & Van, Y.-T. (2006). Microbial synthesis of poly(ε-lysine) and its various
applications. Bioresource Technology, 97(9), 1148–1159.
https://doi.org/10.1016/j.biortech.2004.08.012
Souza, C. E. C., Farias, M. A., Ribeiro, B. D., & Coelho, M. A. Z. (2017). Adding Value to Agro-
industrial Co-products from Canola and Soybean Oil Extraction Through Lipase Production
Using Yarrowia lipolytica in Solid-State Fermentation. Waste and Biomass Valorization, 8(4),
1163–1176. https://doi.org/10.1007/s12649-016-9690-2
Steudler, S., Werner, A., & Walther, T. (2019). It Is the Mix that Matters: Substrate-Specific Enzyme
Production from Filamentous Fungi and Bacteria Through Solid-State Fermentation. In
Steudler, S., Werner, A., Cheng, J. (eds.) Solid State Fermentation. Advances in Biochemical
Engineering/Biotechnology, (Vol. 169, pp. 51–81). Springer, Cham.
https://doi.org/10.1007/10_2019_85
Stredansky, M., & Conti, E. (1999). Xanthan production by solid state fermentation. Process
Biochemistry, 34(6–7), 581–587. https://doi.org/10.1016/S0032-9592(98)00131-9
Suntornsuk, W., Pochanavanich, P., & Suntornsuk, L. (2002). Fungal chitosan production on food
processing by-products. Process Biochemistry, 37(7), 727–729. https://doi.org/10.1016/S0032-
9592(01)00265-5
27
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Tabaraie, B., Ghasemian, E., Tabaraie, T., Rezazarandi, M., & Parvizi, E. (2012). Comparative
evaluation of Cephalosporin-C production in solid state fermentation and submerged liquid
culture. Journal of Microbiology, Biotechnology and Food Sciences, 2(1), 83–94.
https://office2.jmbfs.org/index.php/JMBFS/article/view/7189
Tripathi, M., Diwan, D., Shukla, A. C., Gaffey, J., Pathak, N., Dashora, K., Pandey, A., Sharma, M.,
Guleria, S., Varjani, S., Nguyen, Q. D., & Gupta, V. K. (2024). Valorization of dragon fruit
waste to value-added bioproducts and formulations: A review. Critical Reviews in
Biotechnology, 44(6), 1061–1079. https://doi.org/10.1080/07388551.2023.2254930
Try, S., De-Coninck, J., Voilley, A., Chunhieng, T., & Waché, Y. (2018). Solid state fermentation for
the production of γ-decalactones by Yarrowia lipolytica. Process Biochemistry, 64, 9–15.
https://doi.org/10.1016/j.procbio.2017.10.004
Ueno, H., Shimada, A., Suemitsu, S., Murakami, S., Kitamura, N., Wani, K., Takahashi, Y.,
Matsumoto, Y., Okamoto, M., Fujiwara, Y., & Ishihara, T. (2019). Comprehensive behavioral
study of the effects of vanillin inhalation in mice. Biomedicine & Pharmacotherapy, 115, 108879.
https://doi.org/10.1016/j.biopha.2019.108879
Valdés-Velasco, L. M., Favela-Torres, E., Théatre, A., Arguelles-Arias, A., Saucedo-Castañeda, J. G.,
& Jacques, P. (2022). Relationship between lipopeptide biosurfactant and primary metabolite
production by Bacillus strains in solid-state and submerged fermentation. Bioresource
Technology, 345, 126556. https://doi.org/10.1016/j.biortech.2021.126556
Varghese, S. A., Siengchin, S., & Parameswaranpillai, J. (2020). Essential oils as antimicrobial agents
in biopolymer-based food packaging - A comprehensive review. Food Bioscience, 38, 100785.
https://doi.org/10.1016/j.fbio.2020.100785
Vastrad, B. M., & Neelagund, S. E. (2012). Optimization of Process Parameters for Rifamycin B
Production Under Solid State Fermentation from Amycolatopsis Mediterranean MTCC 14.
International Journal of Current Pharmaceutical Research, 4(2), 101–108.
https://innovareacademics.in/journal/ijcpr/Issues/Vol4Issue2/512.pdf
Wan, C., Fan, X., Lou, Z., Wang, H., Olatunde, A., & Rengasamy, K. R. R. (2022). Iturin: cyclic
lipopeptide with multifunction biological potential. Critical Reviews in Food Science and
Nutrition, 62(29), 7976–7988. https://doi.org/10.1080/10408398.2021.1922355
Wang, Y., Xie, M., Ma, G., Fang, Y., Yang, W., Ma, N., Fang, D., Hu, Q., & Pei, F. (2019). The
antioxidant and antimicrobial activities of different phenolic acids grafted onto chitosan.
Carbohydrate Polymers, 225, 115238. https://doi.org/10.1016/j.carbpol.2019.115238
Wen, T.-C., Li, G.-R., Kang, J.-C., Kang, C., & Hyde, K. D. (2014). Optimization of Solid-state
Fermentation for Fruiting Body Growth and Cordycepin Production by Cordyceps militaris.
Chiang Mai Journal of Science 41(4), 858–872. https://epg.science.cmu.ac.th/ejournal/journal-
detail.php?id=5120
Wu, Y.-S., Ngai, S.-C., Goh, B.-H., Chan, K.-G., Lee, L.-H., & Chuah, L.-H. (2017). Anticancer
Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin
Delivery. Frontiers in Pharmacology, 8, 1–22. https://doi.org/10.3389/fphar.2017.00761
Xia, J., Xu, H., Feng, X., Xu, Z., & Chi, B. (2013). Poly(l-diaminopropionic acid), a novel non-proteinic
amino acid oligomer co-produced with poly(ε-l-lysine) by Streptomyces albulus PD-1. Applied
Microbiology and Biotechnology, 97(17), 7597–7605. https://doi.org/10.1007/s00253-013-4936-4
Xu, D., Yao, H., Xu, Z., Wang, R., Xu, Z., Li, S., Feng, X., Liu, Y., & Xu, H. (2017). Production of ε-
poly-lysine by Streptomyces albulus PD-1 via solid-state fermentation. Bioresource Technology,
223, 149–156. https://doi.org/10.1016/j.biortech.2016.10.032
Yao, D., Ji, Z., Wang, C., Qi, G., Zhang, L., Ma, X., & Chen, S. (2012). Co-producing iturin A and poly-
γ-glutamic acid from rapeseed meal under solid state fermentation by the newly isolated
28
Valdés-Velasco et.al
TECNOCIENCIA CHIHUAHUA, Vol. XX (2026): enero-diciembre, e2152
Bacillus subtilis strain 3-10. World Journal of Microbiology and Biotechnology, 28(3), 985–991.
https://doi.org/10.1007/s11274-011-0896-y
Yilmaz Atay, H. (2019). Antibacterial Activity of Chitosan-Based Systems. In: Jana, S., Jana, S. (eds)
Functional Chitosan (pp. 457–489). Springer Singapore. https://doi.org/10.1007/978-981-15-
0263-7_15
Zeng, X., Yue, C., Ding, Z., Wang, L., Su, Z., Zeng, H., Zhang, B., Li, F., & Zhu, M. (2022). Waste
cooking oil: New efficient carbon source for natamycin production by Streptomyces
gilvosporeus Z8. Process Biochemistry, 118, 294–306.
https://doi.org/10.1016/j.procbio.2022.04.028
Zeng, Y.-J., Yang, H.-R., Wang, H.-F., Zong, M.-H., & Lou, W.-Y. (2019a). Immune enhancement
activity of a novel polysaccharide produced by Dendrobium officinale endophytic fungus
Fusarium solani DO7. Journal of Functional Foods, 53, 266–275.
https://doi.org/10.1016/j.jff.2018.12.038
Zeng, Y.-J., Yang, H.-R., Wu, X.-L., Peng, F., Huang, Z., Pu, L., Zong, M.-H., Yang, J.-G., & Lou, W.-
Y. (2019b). Structure and immunomodulatory activity of polysaccharides from Fusarium
solani DO7 by solid-state fermentation. International Journal of Biological Macromolecules, 137,
568–575. https://doi.org/10.1016/j.ijbiomac.2019.07.019
Zhao, H., Shao, D., Jiang, C., Shi, J., Li, Q., Huang, Q., Rajoka, M. S. R., Yang, H., & Jin, M. (2017).
Biological activity of lipopeptides from Bacillus. Applied Microbiology and Biotechnology,
101(15), 5951–5960. https://doi.org/10.1007/s00253-017-8396-0
Zheng, L., Yu, X., Wei, C., Qiu, L., Yu, C., Xing, Q., Fan, Y., & Deng, Z. (2020). Production and
characterization of a novel alkaline protease from a newly isolated Neurospora crassa through
solid-state fermentation. LWT, 122, 108990. https://doi.org/10.1016/j.lwt.2019.108990
2026 TECNOCIENCIA CHIHUAHUA.
Esta obra está bajo la Licencia Creative Commons Atribución No Comercial 4.0 Internacional.
https://creativecommons.org/licenses/by-nc/4.0/