Discovery of ammosesters by mining the Streptomyces uncialis DCA2648 genome revealing new insight into ammosamide biosynthesis.

ABSTRACT: The ammosamides (AMMs) are a family of pyrroloquinoline alkaloids that exhibits a wide variety of bioactivities. A biosynthetic gene cluster (BGC) that is highly homologous in both gene content and genetic organization to the amm BGC was identified by mining the Streptomyces uncialis DCA2648 genome, leading to the discovery of a sub-family of new AMM congeners, named ammosesters (AMEs). The AMEs feature a C-4a methyl ester, differing from the C-4a amide functional group characteristic to AMMs, and exhibit modest cytotoxicity against a broad spectrum of human cancer cell lines, expanding the structure-activity relationship for the pyrroloquinoline family of natural products. Comparative analysis of the ame and amm BGCs supports the use of a scaffold peptide as an emerging paradigm for the b

SUBMITTER: Luo J 

PROVIDER: S-EPMC8210675 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature