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

Meroterpenoids are mixed polyketide-ter- penoid 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, muta- genesis, and heterologous biosynthesis in the genome- minimized model actinomycete Streptomyces coelicolor provided the S7.6 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 mcl4O resulted in the differential biosynthesis of merochiorin C, suggesting that Mc140 catalyzes an unprecedented iS- membered chloronium-induced macrocydlization reaction converting merochlorin D to merochlorin C. [ABSTRACT FROM AUTHOR]