Metabolic Engineering Strategies for Flavonoid Biosynthesis in Saccharomyces cerevisiae: Current Advances and Future...

Flavonoids are a class of plant secondary metabolites with diverse physiological activities, including antioxidant and anti-inflammatory effects. Growing demand for these compounds now exceeds the capacity of traditional plant extraction methods. Advances in the elucidation of flavonoid biosynthetic pathways, combined with progress in synthetic biology, have enabled the use of engineered microorganisms for sustainable flavonoid production. Saccharomyces cerevisiae, with its well-developed genetic toolkit, high safety profile, and eukaryotic protein modification machinery, has emerged as an ideal chassis for the heterologous biosynthesis of flavonoids. This review systematically outlines the structural classification and biosynthetic pathways of flavonoids, summarizes recent advances in pathway reconstruction, and provides a quantitative comparison of metabolic engineering strategies in S. cerevisiae. We further discuss the key bottlenecks that currently hinder scale‑up from laboratory flasks to industrial bioreactors and propose that future research should focus on intelligent regulatory systems. When combined with rational design of metabolic networks and microbial consortia, such systems can enable adaptive balancing between growth and product synthesis under industrial-scale environmental fluctuations. Collectively, these intelligent engineering strategies will advance S. cerevisiae as an efficient and scalable platform for flavonoid biomanufacturing.