Dihydroquercetin biosynthesis: From plant metabolism to microbial production

Dihydroquercetin (DHQ), a natural dihydroflavonol with a wide range of bioactivities, has garnered increasing attention in pharmaceutical and functional food applications. However, traditional production methods based on plant extraction or chemical synthesis are limited by technical and environmental constraints, posing challenges for large-scale and sustainable production. Microbial biosynthesis using engineered microorganisms has emerged as a promising and sustainable alternative. This review first outlines the structural features, pharmacological functions, and native biosynthetic pathway of DHQ in plants. It then highlights recent advances in the development of microbial cell factories for DHQ production, focusing on key metabolic engineering strategies. These include improving the expression and catalytic efficiency of key enzymes, optimizing cofactor regeneration, enhancing precursor availability, and applying systems biology and multi-omics tools for pathway optimization and bottleneck identification. Finally, current challenges and future directions are discussed, providing insights into strategies for improving DHQ biosynthesis and supporting its broader application.