Discovery and distribution of natural product biosynthesis pathways in the marine actinomycetes Salinispora

基因组挖掘和各种生物信息学技术拓宽了传统的筛选方法，成为发现新的天然产物的重要工具。我们正在开发一种基因组挖掘方法，可以根据适当的生物合成基因的短片段(约600bp)来预测次生代谢物的产生，而不是分析可以超过100kb的完整的生物合成基因簇。这种方法正在应用于四个未组装的盐生孢子基因组序列，其中包括两个新物种“太平洋盐生孢子”的菌株。盐孢子菌是结构多样的次生代谢物的丰富来源，包括多酮、非核糖体肽和PKS/NRPS杂交物。对非核糖体肽合成酶的氨基酸缩合和聚酮合成酶的酰基缩合的保守结构域进行了系统发育分析，不仅评估了四个基因组序列中生物合成途径的类型和数量，而且推断了盐孢子菌物种次生代谢物的进化和生物地理模式。该项目旨在开发一种快速且易于使用的工具，以预测生物合成基因簇在未组装序列数据中的潜在新颖性，并促进新化合物的发现。

Genome mining and various bioinformatic techniques have broadened traditional screening approaches and become important tools for the discovery of new natural products. We are developing a genome mining approach that can be used to predict secondary metabolite production based on short (ca. 600 bp) fragments of the appropriate biosynthetic genes as opposed to the analysis of complete biosynthetic gene clusters, which can exceed 100 kb. This method is being applied to four unassembled Salinispora genome sequences including two strains of the new species “S. pacifica”. Salinospora species are a prolific source of structurally diverse secondary metabolites including polyketides, nonribosomal peptides and PKS/NRPS hybrids. Phylogenetic analyses of conserved domains responsible for amino acid condensation in nonribosomal peptide synthetases and acyl condensation in polyketide synthases are performed not only to assess the type and number of biosynthetic pathways in four genome sequences but also to infer evolutionary and biogeographical patterns of secondary metabolites in Salinospora species. The project intends to develop a fast and easy to use tool to predict the potent novelty of biosynthetic gene clusters in unassembled sequence data and facilitate the discovery of new compounds.