Identification of a gene cluster for telomestatin biosynthesis and heterologous expression using a specific promoter in a clean host.

ABSTRACT: Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers. Difficulties in isolating telomestatin from microbial cultures and in chemical synthesis are bottlenecks impeding the wider use. Therefore, improvement in telomestatin production and structural diversification are required for further utilization and application. Here, we discovered the gene cluster responsible for telomestatin biosynthesis, and achieved production of telomestatin by heterologous expression of this cluster in the engineered Streptomyces avermitilis SUKA strain. Utilization of an optimal promoter was essential for successful production. Gene disruption studies revealed that the tlsB, tlsC, and tlsO-T genes play key roles in telomestatin

SUBMITTER: Amagai K 

PROVIDER: S-EPMC5469769 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature