Recent Advances in The Microbial Synthesis of (-)-α-Bisabolol: Pathway, Enzymes and Strategies.
α-Bisabolol, a natural sesquiterpene alcohol with notable physiological activities, exhibits broad application prospects in the pharmaceutical, cosmetic, and flavor industries. Traditional plant extraction suffers from low efficiency and resource scarcity, while chemical synthesis faces stereoisomerism and environmental issues. In contrast, microbial synthesis overcomes these limitations by utilizing renewable agricultural feedstocks to address plant resource scarcity and enabling highly stereoselective biosynthesis to produce the more bioactive (-)-α-bisabolol. This review summarizes the physiological activities of α-bisabolol, describes its microbial biosynthetic pathway, and focuses on the key enzyme (-)-α-bisabolol synthase. Unlike previous reviews focused on pharmacological effects or chemical synthesis, this review uniquely integrates recent metabolic engineering strategies for enhancing (-)-α-bisabolol production, including chassis cell development, metabolic flux regulation, competitive pathway knockout, cofactors and global regulatory factors optimization, and fermentation scale-up. Finally, current challenges and future directions are discussed, with an emphasis on green biomanufacturing through transporter engineering, enzyme evolution, and subcellular compartmentalization.