Recent advancements in flavonoid production through engineering microbial systems

Flavonoids are a class of polyphenolic compounds found in plants that offer extensive health benefits and have applications in the pharmaceutical, cosmetic, and food industries. Currently, flavonoid production largely depends on plant extraction methods, which face limitations owing to low yields and seasonal and environmental impacts. To address these issues, the potential of microbial fermentation, which leverages advances in metabolic engineering and genetic tools, has been discussed as an innovative alternative to overcome these challenges, thus offering an environmentally friendly and sustainable approach to flavonoid production. However, the integration of complex biosynthesis pathways into microbial systems presents challenges such as the inefficient expression of plant-derived genes, metabolic conflicts, and toxicity or feedback inhibition by accumulated flavonoids within the microbial cells. This comprehensive review highlights recent advancements in engineering strategies to address these challenges, focusing on biotransformation, single-strain fermentation, and co-culture systems, each with its own unique characteristics and potential for optimizing flavonoid production in a cost-effective and scalable manner.