Optimization of biomanufacturing process of high-energy fuel precursorα-bisabolene
α-bisabolene is a sesquiterpene compound mainly found in plant essential oils such as myrrh and lemon.Due to its multi-branched and cyclic structure,its alkylation product bisabolane can be used as a substitute for aviation fuel and has attracted widespread attention at home and abroad.The biosynthesis of α-bisabolene using Saccharomyces cerevisiae as a chassis is a green and sustainable alternative production mode.In this study,aα-bisabolene synthase AgBIS from Abies grandis was expressed in S.cerevisiae with the enhanced key genes of the mevalonate(MVA)pathway.The glucose inducible promoter PHXT1 was used to dynamically downregulate the endogenous squalene synthase and fatty acid synthesis pathway.Further systematic enhancement of the expression of multiple genes in the MVA pathway,cofactor supplementary and ethanol utilization pathway systematically,theα-bisabolene production reached 510 mg/L in the flask.In a 3 L fermenter,the highest reported production ofα-bisabolene was achieved at 120 h with ethanol supplementation,reaching 16.5 g/L.This study provides an effective strategy and research foundation for the efficient biosynthesis of α-bisabolene by microbial cell factories.