Metabolites

Metabolic products produced during fermentation offer a wide array of effects that serve several different markets, including the production of pharmaceuticals, crop protection, and food preservation to name a few. In the development of your fermentation process, what role do your nutrients play when it comes to metabolite production?

What are Metabolites?

Microorganisms produce diverse small molecules, or metabolites, throughout each growth phase that play different roles. Primary metabolites, the molecules that are essential for growth and cellular function¹ (i.e. nucleic acids, proteins, carbohydrates, lipids, etc.) are produced during late lag, log, and early stationary phases. Secondary metabolites, which are not associated with growth or basic cellular functions, are produced during the stationary phase as nutrients deplete. These small molecules provide benefits in terms of cross species interactions or play a role in ecological functions², such as the generation of defensive compounds.

The production of secondary metabolites is a focus of many producers who use fermentation, as bioprocessing of these compounds has a long history of effect on health^3,4 (e.g. antibiotic therapies and anti-tumor/anti-cancer drugs) and novel strategies in biocontrol³ (i.e. macrocyclic insecticides or sesquiterpene fungicides).

Nutrition in Metabolite Production:

Outside of central or primary metabolism, where nutrition plays a crucial role in the physiology of microorganisms (e.g. if your production strain has poor nutrition, your strain will not grow well), nutrition plays a significant role in the production of secondary metabolites. For example, nitrogen-containing compounds can directly influence the regulation of secondary metabolites in Streptomyces⁵. In certain instances, highly concentrated nitrogen sources can inhibit the production of antibiotics^6,7,8 indicating that proper process control and appropriate nutrient concentrations are essential in balancing growth and metabolite production. Here, understanding the metabolic network of production strains becomes crucial to ensure the appropriate nutrition, such as concentrated nitrogen sources, like yeast extracts, can help in the production of antibiotics that are reliant on specific amino acid profiles^9,10,11,12. Yeast extracts have been demonstrated to optimize the production of antifungal metabolites in Streptomyces spp. KN37. Here, of the media components tested, yeast extract provided the most growth, consistent results in terms of antifungal compounds produced, and yeast extract produced enhanced antifungal activity compared to other nitrogen sources^13,14.

In manufacturing bioprocesses for metabolites, it is crucial to understand your organism inside (i. e. native metabolic pathways and networks; any metabolic engineering to optimize productivity) and out (e.g. process conditions, media components, fermentation time, harvest, and recovery). Understanding both sides to your bioprocess will better align with how you can engineer your strain, and ultimately what nutrition is needed to support any changes made. Proper nutrition can and will change with every round of engineering your strain undergoes, which will require iterative rounds of optimization in terms of both bioprocessing (fermentation at scale focused) and bioengineering (strain focused).

How can Sensient BioNutrients Help?

Sensient BioNutrients offers our technical expertise to assist you in optimization of your bioprocess. We utilize our proprietary technology to help understand what nutritional gaps your strain might have that are not readily apparent in terms of typical fermentation KPIs. Our Technical Services Managers are available to support with process scale-up, helping troubleshoot issues in manufacturing, and can offer their expertise for up and downstream processes, as well as microbial contamination control. This technical support extends to our R&D team, with our state-of-the-art laboratory, fully equipped to identify the right nutrients for your process. Sensient BioNutrients is ready to support your facility with our proprietary Process Economics Calculator to demonstrate an optimized process in terms of direct and indirect costs of production. Reach out to your Sensient BioNutrients Account Manager for more information!

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Sources

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2. Abdel-Aziz, S. M., M. M. Abo Elsoud, A. A. H. Anise. 2017. Chapter 2 – Microbial Biosynthesis: A Repertory of Vital Natural Products. Handbook of Food Bioengineering pgs. 25-54.
3. Fouillaud, M. and L. Dufossé. 2022. Microbial Secondary Metabolism and Biotechnology. Microorganisms. 10 (1): 123. DOI: 10.3390/microorganisms10010123
4. Monciardini, P. et al. 2014. Discovering new bioactive molecules from microbial sources. Microbial Biotechnology 7(3): 209-220.
5. Krysenko, S. 2023. Impact of nitrogen-containing compounds on secondary metabolism in Streptomyces spp. – A source of metabolic engineering strategies. SynBio 1 (3): 204-225.
6. Brana, A. F., A. L. S. Demain. 1988. Nitrogen control of antibiotic biosynthesis in actinomycetes. Nitrogen Source Control of Microbial Processes, pgs. 99-119.
7. Hobbs, G. et al. 1992. An integrated approach to studying regulation of production of the antibiotic methylenomycin by Streptomyces coelicolor A3. Journal of Bacteriology. 174, 1487-1497.
8. Krysenko, S. and W. Wohlleben. 2022. Polyamine and ethanolamine metabolism in bacteria as an important component of nitrogen assimilation for survival and pathogenicity. Medical Sciences. 10 (3): 40. https://doi.org/10.3390/medsci10030040
9. Hodgson, D. A. 2000. Primary metabolism and its control in streptomycetes: A most unusual group of bacteria. Advances in Microbial Physiology. 42: 47-238
10. Hu, D. S. et al. 1999. The expression of the trpD, trpC, and trpBA genes of Streptomyces coelicolor A3 is regulated by growth rate and growth phase but not by feedback repression. Molecular Microbiology. 32: 869-880.
11. Mast, Y., et al. 2011. Characterization of the ‘pristinamycin supercluster’ of Streptomyces pristinaespiralis. Microbial Biotechnology. 4: 192-206.
12. Leite, C. A., A. P. Cavallieri, and M. L. Araujo. 2013. Enhancing effect of lysine combined with other compounds on cephamycin C production in Streptomyces clavuligerus. BMC Microbiology. 13: 296.
13. Yang, X., et al. 2025. Optimization of fermentation conditions to increase the production of antifungal metabolites from Streptomyces sp. KN37. Microbial Cell Factories. 24:26, 1-13
14. Liu, H. et al. 2020. Medium optimization for spore production of a straw-cellulose degrading actinomyces strain under solid-state fermentation using response surface method. Sustainability. 12 (21): 8893