Microbial biosynthesis of stilbenoids: A comprehensive review

Stilbenoids represent a valuable class of plant polyphenols with significant pharmacological activities, such as anticancer, anti-inflammatory, and antioxidant effects, leading to a growing market demand. Traditional plant extraction or chemical synthesis faces challenges including low yield, process complexity, and environmental concerns. Microbial biosynthesis has consequently emerged as a transformative and eco-friendly alternative. This review provides a comprehensive analysis of recent advances in microbial stilbenoid production, including metabolic engineering strategies, pathway optimization, enzyme engineering, and host chassis development. The production milestones and current synthetic capabilities for key stilbenes (e.g., resveratrol, pterostilbene) are comprehensively summarized. Moreover, fundamental bottlenecks were discussed, particularly the catalytic limitations of key stilbene synthases, metabolic flux imbalances, and the lack of efficient enzymatic toolkits for post-modifications. Finally, we propose that the integration of emerging technologies, such as artificial intelligence-assisted enzyme design and systematical metabolic engineering will play a pivotal role in constructing robust microbial cell factories for the efficient and sustainable production of diverse stilbenoids.