Genomic sequence-based discovery of novel angucyclinone antibiotics from marine Streptomyces sp. W007

Abstract

A large number of novel bioactive compounds were discovered from microbial secondary metabolites based on the traditional bioactivity screenings. Recent fermentation studies indicated that the crude extract of marine Streptomyces sp. W007 possessed great potential in agricultural fungal disease control against Phomopsis asparagi, Polystigma deformans, Cladosporium cucumerinum, Monilinia fructicola, and Colletotrichum lagenarium. To further evaluate the biosynthetic potential of secondary metabolites, we sequenced the genome of Streptomyces sp. W007 and analyzed the identifiable secondary metabolite gene clusters. Moreover, one gene cluster with type II PKS implied the possibility of Streptomyces sp. W007 to produce aromatic polyketide of angucyclinone antibiotics. Therefore, two novel compounds, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro-benz[α]anthracene and kiamycin with potent cytotoxicities against human cancer cell lines, were isolated from the culture broth of Streptomyces sp. W007. In addition, other four known angucyclinone antibiotics were obtained. The gene cluster for these angucyclinone antibiotics could be assigned to 20 genes. This work provides powerful evidence for the interplay between genomic analysis and traditional natural product isolation research.