Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica.

ABSTRACT: Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a "push-pull" strategy was adopted to increase taxadiene production by 234%. Then taxadiene synthase was fused with five solubilizing tags respectively, leading a maximum increase of 62.3% in taxadiene production when fused with SUMO. Subsequently, a multi-copy iterative integration method was used to further increase taxadiene titer, achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration. Finally, the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentat

SUBMITTER: Xu M 

PROVIDER: S-EPMC10196790 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature