Co-biosynthesis of germacrene A, a precursor of β-elemene, and lycopene in engineered Escherichia coli.

β-Elemene is the major component of a traditional Chinese medicine (Rhizoma Curcumae) for cancer treatment, and plant extraction is the major methods currently. Biosynthesis of β-elemene is a promising and attractive route due to its advantages, including environmentally friendly processes, renewable resources, and sustainable development. In this research, biosynthesis of germacrene A, direct precursor of β-elemene, in Escherichia coli was successfully performed and 11.99 mg/L germacrene A was obtained. Thereafter, a cobiosynthesis system for germacrene A and lycopene, another kind of isoprenoid, was constructed. Furthermore, the cultivation conditions were optimized. The germacrene A production was increased to the highest level reported to date, 364.26 mg/L, threefold increase to the strain with only germacrene A production. The cobiosynthesis system was suggested to promote the metabolic flux for germacrene A production. This research enabled germacrene A production in E. coli, and it highlights the promoting mechanism of the cobiosynthesis system for two chemicals which are both belonging to isoprenoids. KEY POINTS : • Co-production of germacrene A and lycopene in E. coli. • Promoting mechanism of cobiosynthesis of two isoprenoid compounds in E. coli. • Shake-flask production of germacrene A reached to the highest 364.26 mg/L in E. coli.