Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412.

ABSTRACT: Tautomycetin (TMC) is a linear polyketide metabolite produced by Streptomyces sp. CK4412 that has been reported to possess multiple biological functions including T cell-specific immunosuppressive and anticancer activities that occur through a mechanism of differential inhibition of protein phosphatases such as PP1, PP2A, and SHP2. We previously reported the characterization of the entire TMC biosynthetic gene cluster constituted by multifunctional type I polyketide synthase (PKS) assembly and suggested that the linear form of TMC could be generated via free acid chain termination by a narrow TMC thioesterase (TE) pocket. The modular nature of the assembly presents a unique opportunity to alter or interchange the native biosynthetic domains to produce targeted variants of TMC. Herein, we r

SUBMITTER: Tripathi A 

PROVIDER: S-EPMC4939285 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature