Collagen Science Update – April 2024 Edition

Fermentation-Based Collagen

Collagen is a major and structurally essential protein abundantly found in the human body, primarily within the skin, tissues, nails, hair, bones, tendons, and cartilage (Bhadra et al., 2021; Añazco et al., 2023). Human collagen production decreases with age, resulting in reduced skin elasticity, firmness, and moisture, as well as unwanted changes in joint health. Therefore, collagen is a desirable ingredient for food, pharmaceutical, nutraceutical, and cosmetic industries to support skin, joint, and overall health (Añazco et al., 2023). In addition to being naturally produced by the human body, collagen can be derived from a variety of different animal source materials, such as pig, sheep, cow, or fish (Añazco et al., 2023). As many industries are looking for innovative ways to produce more sustainable and animal-free products, the development of fermentation-based collagen is a favorable alternative.

Fermentation-based collagen involves the manipulation of bacteria, such as E. coli, to produce collagen-like proteins with the characteristic triple-helix scaffold conformation that is present in animal-based collagen proteins (Peng et al., 2012; Yu et al., 2014; Peng et al., 2015; Bhadra et al., 2021). There are 28 different types of collagens found naturally within the human body that have been characterized with this structure (Bhadra et al., 2021; Añazco et al., 2023; Guo et al., 2023). Unlike collagen derived from human or animal sources, fermentation-based collagen protein does not contain the post-translationally modified amino acid, hydroxyproline (Hyp), which attributes to the stability of the protein (Yu et al., 2014). Despite the absence of Hyp, many fermentation-based collagen proteins are found to be highly stable at 35–38°C, making them readily producible recombinant products that can be purified for further use (Peng et al., 2012; Yu et al., 2014; Peng et al., 2015). The synthetic production of collagen through microbes is limited by its capability of post-translational modifications and therefore, many producers have adopted the genetic manipulation of yeast and plant systems to increase growth rates and ease of industrial-scale production (Peng et al., 2015; Bhadar et al., 2021; Gomes et al., 2022). However, in 2012 Peng et al. established that fermentation-based collagen can be produced in large quantities from E. coli, with average production levels yielding greater quantities than conventionally produced collagen from mammalian yeast expression systems. Fermentation-based collagen can also be referred to as recombinant collagen-like protein, bacteria-based collagen, bacterial collagen, non-animal collagen, or plant-based collagen, as cited in the scientific literature. 

Fermentation-Based Collagen Applications

The demand for non-animal or plant-based collagen is becoming increasingly common in today’s market due to different ethical, religious, or health-conscious reasons, such as worries related to bovine spongiform encephalopathy and foot-and-mouth disease (Peng et al., 2012; Peng et al., 2015; Steele, 2022). Each of the 28 types of collagens exhibit a distinct purpose, making collagen a versatile protein for various applications, including food, nutraceuticals, cosmetics, and tissue engineering (Bhadra et al., 2021). For example, type 21 collagen has been identified as a clinical precursor to types I and III which are responsible for providing strength, elasticity, and water retention capacity (Añazco et al., 2023). Type 21 collagen has been successfully developed using new biotechnologies as the “first vegan bioidentical human collagen designed for skincare” (SCC, 2022). In addition, the limited biological interactions of fermentation-based collagen allow for potential use in clinical applications such as wound management or adhesion prevention (Peng et al., 2012). 

This edition highlights three recent publications that provide new insights into the use of fermentation-based collagen supplements for skincare and other potential health applications.

Oral Supplementation of Vegan Collagen Biomimetic Has Beneficial Effects on Human Skin Physiology: A Double-blind, Placebo-controlled Study

A randomized controlled trial conducted by Lin et al. (2024) evaluated the roles of vegan collagen and its skin beautifying effects on the human body. Ninety adult participants (80 female, 10 male) were enrolled and randomly divided into three groups: placebo (n=30), vegan collagen (n=30), and fish collagen (n=30). The vegan collagen used in this study contained 5 g of VeCollal®, comprised of fermented amino acids obtained from plant-based materials and biosynthesized by the bacterium, Corynebacterium glutamicum. Participants were instructed to consume one sachet of test product, daily for eight weeks. Skin conditions were measured at baseline (week-0), week-4, and week-8. It was observed that VeCollal® significantly improved skin collagen density and elasticity, significantly reduced wrinkles and improved skin texture and pore appearance, and significantly increased skin hydration and lightness. This study concluded that fermentation-based collagen is a new type of collagen biomimetic produced without animal sources, rich in asiaticoside and ginsenosides, with clinical benefits on human skin.

Access to the study: 

Reference: Lin, Y.K., Liang, C.H., Lin, Y.H., Lin, T.W., Vázquez, J.J., van Campen, A., Chiang, C.F. (2024). Oral Supplementation of Vegan Collagen Biomimetic Has Beneficial Effects on Human Skin Physiology: A Double-blind, Placebo-controlled Study. Journal of Functional Foods, 112(105955). 

Status and Developmental Trends in Recombinant Collagen Preparation Technology

A literature review published by Guo et al. (2023) provides an extensive overview of current genetic engineering techniques and production methods employed to manufacture recombinant collagen and the quality control measures required. Recombinant collagen has been successfully produced via different expression systems, including various human cells, yeast, bacteria, and transgenic animals and plants. Bacterial, yeast, and insect cell expression systems are commonly used for their ease of industrial-scale production, traceable origins, and clear culture history. The cost-effective E. coli expression system is the current leading method of production responsible for approximately 40% of clinically used recombinant proteins. The fermentation of E. coli can yield recombinant type III humanized collagen, which may be influenced by multiple factors such as medium composition, strain quality and size, culture temperature, pH, and oxygen concentration. Recombinant collagen has significant potential for applications in healthcare products, cosmetics, and biomedicine due to its excellent biocompatibility, controllable quality, and low risk of viral contamination. However, its large-scale use is hindered by insufficient post-translational modifications (i.e., hydroxylation) in prokaryotic and eukaryotic expression systems where recombinant collagen cannot achieve the same level of hydroxylation as naturally derived collagen. Co-expression of collagen and hydroxylase is crucial for producing recombinant collagen that closely resembles natural human collagen. In addition, market supervision and access to recombinant collagen products may pose problems as there is a lack of consensus among regulatory agencies regarding large-scale production and clinical application. Despite these challenges, advances in genetic engineering technologies have the potential to reduce research and development costs, leading to more affordable, higher-output recombinant collagen with improved properties.

Access to the study: 

Reference: Guo, X., Ma, Y., Wang, H., Yin, H., Shi, X., Chen, Y., Gao, G., Sun, L., Wang, J., Wang, Y., & Fan, D. (2023). Status and developmental trends in recombinant collagen preparation technology. Regenerative Biomaterials, 11(rbad106). 

Assessing Malaysian Firms’ Intention to Use Recombinant Collagen-Like Protein in Collagen Products

A study conducted by Duasa et al. (2023) used a Technology Acceptance Model (TAM), a theoretical model that explains and predicts the behaviors in adopting new technology, to assess the prospect of using recombinant collagen-like protein from a producer’s point of view. Seventeen different industries in Peninsula Malaysia that are involved in the production of collagen products were surveyed and provided questionnaires. Based on the results of the completed questionnaires, direct positive and significant relations between “perceive ease of use” and “attitude toward”, “perceive ease of use” and “perceived usefulness”, “attitude toward” and “behavioral intention”, and “perceived usefulness” and “behavioral intention” of producing recombinant collagen-like protein products were observed. These results suggest a favorable recognition to using alternative sources of collagen that are environmentally friendly and promote sustainable development. 

Access to the study: 

Reference: Duasa, J., Radzman, N.A.M., Thaker, M.A.M.T. (2023). Assessing Malaysian Firms’ Intention to Use Recombinant Collagen-Like Protein in Collagen Products. IOP Conference Series: Earth and Environmental Science, 1165(012008).  

Bottom Line 

There is an increasing trend among consumers who are looking for more sustainable, environmentally friendly, animal-free, and ethically sourced products. While traditional sources of collagen include animals, fermentation-based collagen offers a sustainable alternative. With the emergence of fermentation or recombinant technology, stable collagen can be produced to create collagen products that have applications in skin health, joint support, and overall wellbeing, while meeting the consumer demand for non-animal collagen.   


Añazco, C., Ojeda, P. G., & Guerrero-Wyss, M. (2023). Common Beans as a Source of Amino Acids and Cofactors for Collagen Biosynthesis. Nutrients, 15(21):4561.

Bhadra, B., Sakpal, A., Patil, S., Patil, A., Date, A., Prasad, V., & Dasgupta, S. (2021). A Guide to Collagen Sources, Applications and Current Advancements. Systematic Bioscience and Engineering, 1(2):67–8. 

SCC (Society of Cosmetic Chemists) (2022), Geltor HumaColl21®Biomimetic Vegan Human Collagen. Retrieved 2024 May 02. Available from: 

Gomes, V., Salgueiro, S.P. (2022). From small to large-scale: a review of recombinant spider silk and collagen bioproduction. Discover Materials, 2(3). 

Peng, Y.Y., Howell, L., Stoichevska, V., Werkmeister, J.A., Dumsday, G.J., & Ramshaw, J.A. (2012). Towards scalable production of a collagen-like protein from Streptococcus pyogenes for biomedical applications. Microbial Cell Factories, 11, 146. 

Peng, Y.Y., Stoichevska, V., Vashi, A., Howell, L., Fehr, F., Dumsday, G.J., Werkmeister, J.A., & Ramshaw, J.A. (2015). Non-animal collagens as new options for cosmetic formulation. International Journal of Cosmetic Science, 37(6):636–641. 

Steele, C. (2022). Collagen: a review of clinical use and efficacy. Nutritional Medicine Journal, 1(2):12–36.

Yu, Z., An, B., Ramshaw, J.A., & Brodsky, B. (2014). Bacterial collagen-like proteins that form triple-helical structures. Journal of Structural Biology, 186(3):451–461.