High efficient production of plant flavonoids by microbial cell factories: Challenges and opportunities

Plant flavonoids are secondary metabolites containing a benzo-gamma-pyrone structure, which are widely present in plants and have a variety of physiological and pharmacological activities. However, current flavonoid production from plant extraction or chemical synthesis does not meet the requirements of green and sustainable development. Fortunately, microbial synthesis of flavonoids has shown the potential for large-scale production with the advantages of being controllable and environmentally friendly, and a variety of microorganisms have been developed as microbial cell factories (MCFs) to synthesize plant flavonoids owing to the feasibility of genetic manipulations. However, most of MCFs have not yet been commercialized and industrialized because of the challenges posed by unbalanced metabolic flux among various pathways and conflict between cell growth and production. Here, strategies for coping with the challenges are summarized in terms of enzymes, pathways, metabolic networks, host cells. And combined with protein structure prediction, de novo protein design, artificial intelligence (AI), biocatalytic retrosynthesis, and intelligent stress resistance, it provides new insights for the high efficient production of plant flavonoids and other plant natural products in MCFs.

Automated summary

Plant flavonoids are secondary metabolites with various physiological and pharmacological activities. Current production methods from plants or chemicals do not meet the requirements of green and sustainable development. Microbial synthesis of flavonoids has shown potential for large-scale production, but challenges such as metabolic flux imbalance and conflict between cell growth and production hinder commercialization of microbial cell factories. Strategies discussed in this article, combined with protein structure prediction, de novo protein design, artificial intelligence, biocatalytic retrosynthesis, and intelligent stress resistance, provide insights for efficient production of plant flavonoids and other natural products in microbial cell factories.