Improvement of FK506 production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis.

ABSTRACT:

Background

FK506, a macrolide mainly with immunosuppressive activity, can be produced by various Streptomyces strains. However, one of the major challenges in the fermentation of FK506 is its insufficient production, resulting in high fermentation costs and environmental burdens. Herein, we tried to improve its production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis.

Results

First, basing on the genome sequencing and analysis, putative competitive pathways were deleted. A better parental strain L19-2 with increased FK506 production from 140.3 to 170.3 mg/L and a cleaner metabolic background was constructed. Subsequently, the FK506 biosynthetic gene cluster was refactored by in-situ promoter-substitution strategy basing on the regulat

SUBMITTER: Wu QB 

PROVIDER: S-EPMC8383387 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature