Daniel W. Udwary1, Lisa Zeigler1, Ratnakar N. Asolkar1, Vasanth Singan2, Alla Lapidus2, William Fenical1, Paul R. Jensen1, Bradley S. Moore1,3
1*Scripps Institution of Oceanography and
2Department of Energy, Joint Genome Institute–Lawrence Berkeley National Laboratory, Walnut Creek, CA 94598
3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093-0204; and
Tóm tắt
Recent fermentation studies have identified actinomycetes of the marine-dwelling genus
Salinispora
as prolific natural product producers. To further evaluate their biosynthetic potential, we sequenced the 5,183,331-bp
S. tropica
CNB-440 circular genome and analyzed all identifiable secondary natural product gene clusters. Our analysis shows that
S. tropica
dedicates a large percentage of its genome (≈9.9%) to natural product assembly, which is greater than previous
Streptomyces
genome sequences as well as other natural product-producing actinomycetes. The
S. tropica
genome features polyketide synthase systems of every known formally classified family, nonribosomal peptide synthetases, and several hybrid clusters. Although a few clusters appear to encode molecules previously identified in
Streptomyces
species, the majority of the 17 biosynthetic loci are novel. Specific chemical information about putative and observed natural product molecules is presented and discussed. In addition, our bioinformatic analysis not only was critical for the structure elucidation of the polyene macrolactam salinilactam A, but its structural analysis aided the genome assembly of the highly repetitive
slm
loci. This study firmly establishes the genus
Salinispora
as a rich source of drug-like molecules and importantly reveals the powerful interplay between genomic analysis and traditional natural product isolation studies.
