Udwary Daniel W, Zeigler Lisa, Asolkar Ratnakar N, Singan Vasanth, Lapidus Alla, Fenical William, Jensen Paul R, Moore Bradley S
Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0204, USA.
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10376-81. doi: 10.1073/pnas.0700962104. Epub 2007 Jun 11.
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 ( approximately 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.
近期的发酵研究已确定,海洋栖居的盐孢菌属放线菌是丰富的天然产物生产者。为进一步评估其生物合成潜力,我们对5,183,331 bp的热带盐孢菌CNB - 440环状基因组进行了测序,并分析了所有可识别的次生天然产物基因簇。我们的分析表明,热带盐孢菌将其基因组的很大一部分(约9.9%)用于天然产物组装,这一比例高于之前的链霉菌基因组序列以及其他产生天然产物的放线菌。热带盐孢菌基因组具有每个已知正式分类家族的聚酮合酶系统、非核糖体肽合成酶以及几个混合簇。尽管有一些簇似乎编码了先前在链霉菌物种中鉴定出的分子,但17个生物合成位点中的大多数都是新的。文中给出并讨论了关于推定和观察到的天然产物分子的具体化学信息。此外,我们的生物信息学分析不仅对多烯大环内酰胺盐孢菌素A的结构解析至关重要,而且其结构分析有助于高度重复的slm位点的基因组组装。这项研究牢固地确立了盐孢菌属作为类药物分子丰富来源的地位,并且重要的是揭示了基因组分析与传统天然产物分离研究之间强大的相互作用。