Fermentation for Flavonoids and Phenolics

As a leading CDMO in fermentation, BOC Sciences provides one-stop services to manufacture microbial fermented products such as flavonoids and phenolics. We are able to support the strains development or fermentation process optimization to biosynthesize the desired natural products and to scale up production. Our comprehensive platform is dedicated to meet the needs of customers in industries including pharmaceutical, food, nutraceutical, cosmetic and many others.

Introduction of Flavonoids and Phenolics

Phenolis belong to the aromatic compounds in which hydrogen atoms in the benzene ring are replaced by hydroxyl groups. These compounds have the potential for antioxidant activity due to their high reactivity of hydroxyl substitution and their ability to phagocytose free radicals. Flavonoids is a kind of yellow pigments derived from flavones (2-phenylchromogens) as parent nuclei, including isomers of flavones and their hydrogenation and reduction products, that is, a series of compounds with C6-C3-C6 as the basic carbon frame. Flavonoids are the largest group of naturally occurring phenolic compounds. For now, industrial production of flavonoids and phenolics is mainly through the extraction from different plant components. This production method is limited by season and process. Moreover, the product purity is not high and the price is expensive. Therefore, it is promised to become a method that produces these compounds skeleton by means of fermentation engineering.

Fermentation Production of Flavonoids and Phenolics

Flavonoids are a series of plant secondary metabolites derived from phenylpropane metabolic pathway through flavonoid synthesis pathway. Flavonoid synthesis pathway is an important branch of phenylalanine metabolism pathway. There are some key enzymes involved including phenylalanine ammonialyase (PAL) and cinnamate hydroxylase (C4H), 4-coumaric acid-Coenzyme A ligase (4CL), Chalcone synthase (CHS), chalcone isomerase (CHI). By introducing these key enzymes into E. coli or yeast, the restriction of flavonoids synthesis from phenylalanine can be circumvented and higher flavonoid skeleton yield can be achieved.

Hydrolysis of complex enzyme systems including cellulose hydrolase, lignin hydrolase, pectin hydrolase, etc. produced by microbial fermentation can destroy the dense structure of cell wall fiber components or remove the covalent bonds between polyphenols and other substances. This process promotes the release and transformation of phenolics, thereby affecting the change of their biological activity. Researchers used Aspergillus Niger and Rhizopus oligopolyticus to ferment the by-products of fruit juice processing. And the content of phenolics and flavonoids in the residue were increased greatly, accompanied with the ability of scavenging free radical.

Advantages of Fermentation for Flavonoids and Phenolics

The method of chemical synthesis involves the use of chemical reagents and strict reaction conditions, and it is easy to produce solvent residue. The prepared flavonoids and phenolics are easy to cause safety problems when used in food, health care products, cosmetics and other products. Therefore, the use of microorganisms to synthesize flavonoids and phenolics has attracted more and more attention. As a heterologous synthesis method using synthetic biology tools in microorganisms, fermentation to produce flavonoids and phenolics has the advantages of environmental friendliness and resource saving, and meets the application prospect of sustainable development.

Application of Fermented Flavonoids

There are many compounds with medicinal value in flavonoids, which can be used for the prevention and treatment of cardiovascular and cerebrovascular diseases, such as cerebral hemorrhage, coronary heart disease, and angina pectoris. Many flavonoids also have antitussive, expectorant, anti-asthmatic and anti-bacterial activities. With the development of synthetic biology and metabolic engineering, such as dihydroflavones, flavones, isoflavones, flavonols, anthocyanidins and flavanones can be synthesized by engineering yeast, E. coli or other microorganisms. On this basis, they can also be modified by methylase or glycosylase to increase new biological activities. These compounds have antioxidant, anti-inflammatory, anti-tumor, improve blood circulation and other physiological functions, which have broad application prospects in health care products, cosmetics and medicine.

Reference

Septembre-Malaterre A. et al. as a source of nutritional compounds and phytochemicals: Changes in bioactive compounds during lactic fermentation. Food Res Int. 2018, 104:86-99.