Merochlorins A-D, Cyclic Meroterpenoid Antibiotics Biosynthesized in Divergent Pathways with Vanadium-Dependent Chloroperoxidases

Citation:
Kaysser, L, Bernhardt P, Nam SJ, Loesgen S, Ruby JG, Skewes-Cox P, Jensen PR, Fenical W, Moore BS.  2012.  Merochlorins A-D, Cyclic Meroterpenoid Antibiotics Biosynthesized in Divergent Pathways with Vanadium-Dependent Chloroperoxidases. Journal of the American Chemical Society. 134:11988-11991.

Date Published:

Jul

Keywords:

cloning, gene-cluster, heterologous expression, natural-products, streptomyces

Abstract:

Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures of four new meroterpenoid antibiotics, merochlorins A-D, produced by the marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis, and heterologous biosynthesis in the genome-minimized model actinomycete Streptomyces coelicolor provided the 57.6 kb merochlorin gene cluster that contains two genes encoding rare bacterial vanadium-dependent haloperoxidase (VHPO) genes. Pathway expression of two different fosmid clones that differ largely by the presence or absence of the VHPO gene mcl40 resulted in the differential biosynthesis of merochlorin C, suggesting that Mcl40 catalyzes an unprecedented 15-membered chloronium-induced macrocyclization reaction converting merochlorin D to merochlorin C.

Notes:

n/a

Website

DOI:

10.1021/ja305665f