Lawrence Berkeley National Laboratory

Recent fermentation studies have identified actinomycetes of the marine-dwelling genus Salinispora as prolific natural product producers. To further evaluate their biosynthetic potential, we analyzed all identifiable secondary natural product gene clusters from the recently sequenced 5,184,724 bp S. tropica CNB-440 circular genome. Our analysis shows that biosynthetic potential meets or exceeds that shown by previous Streptomyces genome sequences as well as other natural product-producing actinomycetes. The S. tropica genome features nine polyketide synthase systems of every known formally classified family, non-ribosomal peptide synthetases and several hybrid clusters. While a few clusters appear to encode molecules previously identified in Streptomyces species, the majority of the 15 biosynthetic loci are novel. Specific chemical information about putative and observed natural product molecules is presented and discussed. In addition, our bioinformatic analysis was critical for the structure elucidation of the novel polyenemacrolactam salinilactam A. This study demonstrates the potential for genomic analysis to complement and strengthen traditional natural product isolation studies and firmly establishes the genus Salinispora as a rich source of novel drug-like molecules.