Engineering plant hosts for high-efficiency accumulation of flavonoids: Advances, challenges and perspectives.

Flavonoids are a vital class of compounds that contribute to plant resistance and also beneficial to human health. Increasing plant flavonoid content or enabling the synthesis of specific flavonoids can enhance plant resistance to biotic and abiotic stress while augmenting their nutritional value, thereby supporting sustainable agricultural practices. Although numerous studies have focused on increasing flavonoid content in plants, traditional engineering strategies lack the precision required to selectively regulate the synthesis of individual flavonoids. In contrast, systems and synthetic biology provide innovation approaches to address these challenges. Here, we summarize research on the distribution, biosynthetic pathways, and transcriptional regulation of flavonoids in plants. Subsequently, we analyze current progress in altering plant-flavonoid content, including transcriptional regulation, transporter engineering, and lifting rate-limiting steps. Additionally, we summarize potential strategies for precisely altering flavonoid biosynthetic pathways, including the selection of ideal hosts, designating artificially modifiable genetic elements, accelerating enzyme evolution by protein engineering, enhancing cascade biocatalysis and metabolic flux, and rebalancing metabolic fluxes. Finally, we discuss current limitations and prospects for building a next-generation plant hosts for high-efficiency flavonoid biosynthesis. This review aims to provide theoretical guidance for the modification and reconstruction of flavonoid biosynthesis in plants using systems and synthetic biology approaches.