Bioactivity-Guided Genome Mining Reveals the Lomaiviticin Biosynthetic Gene Cluster in Salinispora tropica

Document Type

Article

Publication Date

5-27-2013

Abstract

The use of genome sequences has become routine in guiding the discovery and identification of microbial natural products and their biosynthetic pathways. In silico prediction of molecular features, such as metabolic building blocks, physico-chemical properties or biological functions, from orphan gene clusters has opened up the characterization of many new chemo- and genotypes in genome mining approaches. Here, we guided our genome mining of two predicted enediyne pathways in Salinispora tropica CNB-440 by a DNA interference bioassay to isolate DNA-targeting enediyne polyketides. An organic extract of S. tropica showed DNA-interference activity that surprisingly was not abolished in genetic mutants of the targeted enediyne pathways, ST_pks1 and spo. Instead we showed that the product of the orphan type II polyketide synthase pathway, ST_pks2, is solely responsible for the DNA-interfering activity of the parent strain. Subsequent comparative metabolic profiling revealed the lomaiviticins, glycosylated diazofluorene polyketides, as the ST_pks2 products. This study marks the first report of the 59 open reading frame lomaiviticin gene cluster (lom) and supports the biochemical logic of their dimeric construction through a pathway related to the kinamycin monomer. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Publication Title

ChemBioChem

Volume

14

Issue

8

First Page

955

Last Page

962

Digital Object Identifier (DOI)

10.1002/cbic.201300147

PubMed ID

23649992

ISSN

14394227

E-ISSN

14397633

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