Reprogramming for a Robust Chassis toward Efficient Biosynthesis of (-)-α-Bisabolol.

(-)αBisabolol, a monocyclic susquiterpene alcohol, has been widely used in the fields of food, medicine, and biofuel. Recently, the rapid development of synthetic biology has offered a sustainable route for the production of (-)αbisabolol by microbial cell factories. Even though efficient biosynthesis of (-)αbisabolol has been achieved in with the highest titer of 23.4 g/L, the possible infection risk by the bacteriophage makes unsuitable to act as the most robust chassis. Herein, we optimized the MVA pathway of and fused farnesyl diphosphate synthase (ERG20), with bisabolol synthase for efficient production of (-)αbisabolol. Through the engineering of cofactor NADPH, molecular chaperone, and transcription factors, we obtained the robust (-)αbisabolol-producing strain, KB-30. Finally, the highly efficient production of (-)-α-bisabolol was achieved in a 5 L fed-batch fermenter, giving a titer of 32.8 g/L and a space-time yield of 283 mg/L/h. This work represents the highest production of (-)-α-bisabolol to date and provides new insights for efficient terpenoid biosynthesis.