Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica
Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica
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DOI：
10.1073/pnas.0700962104
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发表时间：
2007-06-19
影响因子：
11.1
通讯作者：
Moore, Bradley S.
中科院分区：
文献类型：
--
作者：
Udwary, Daniel W.;Zeigler, Lisa;Moore, Bradley S.
最近的发酵研究发现，海洋生活的盐生孢属的放线菌是多产的天然产物。为了进一步评估它们的生物合成潜力，我们对5,183,331个碱基的热带葡萄球菌CNB-440循环基因组进行了测序，并对所有可识别的次生天然产物基因簇进行了分析。我们的分析表明，热带链霉菌将很大比例的基因组(约9.9%)用于天然产物组装，这一比例高于以往的链霉菌基因组序列以及其他产生天然产物的放线菌。热带葡萄球菌基因组具有每个已知正式分类家族的聚酮合成酶系统、非核糖体多肽合成酶和几个杂交簇。虽然有几个簇似乎编码了以前在链霉菌物种中发现的分子，但17个生物合成基因座中的大多数都是新的。对推测和观察到的天然产物分子的具体化学信息进行了介绍和讨论。此外，我们的生物信息学分析不仅对阐明多烯大内酰胺盐内酰胺A的结构至关重要，而且它的结构分析有助于高度重复的SLM基因座的基因组组装。这项研究坚定地确立了盐生孢属作为类药物分子的丰富来源，并重要地揭示了基因组分析和传统的天然产物分离研究之间的强大相互作用。
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 (approximate to 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.