纳他霉素高产菌株Streptomyces gilvosporeus F607基因组及其生物合成基因簇分析

Analysis of genome sequence and natamycin biosynthetic gene cluster on high producing strain Streptomyces gilvosporeus F607

摘要:

【背景】纳他霉素(Natamycin)是一种天然、广谱、高效的多烯大环内酯类抗真菌剂，褐黄孢链霉菌(Streptomyces gilvosporeus)是一种重要的纳他霉素产生菌。目前S. gilvosporeus基因组序列分析还未有报道，限制了该菌中纳他霉素及其他次级代谢产物合成及调控的研究。【目的】解析纳他霉素高产菌株S. gilvosporeus F607的基因组序列信息，挖掘其次级代谢产物基因资源，为深入研究该菌株的纳他霉素高产机理及生物合成调控机制奠定基础。【方法】利用相关软件对F607菌株的基因组序列进行基因预测、功能注释、进化分析和共线性分析，并预测次级代谢产物合成基因簇；对纳他霉素生物合成基因簇进行注释分析，比较分析不同菌种中纳他霉素生物合成基因簇的差异；分析预测S. gilvosporeus F607中纳他霉素生物合成途径。【结果】F607菌株基因组总长度为8 482 298 bp，(G+C)mol%为70.95%，分别在COG、GO、KEGG数据库提取到5 062、4 428、5 063个基因的注释信息。同时，antiSMASH软件预测得到29个次级代谢产物合成基因簇，其中纳他霉素基因簇与S. natalensis、S. chattanoogensis等菌株的纳他霉素基因簇相似性分别为81%和77%。除2个参与调控的sngT和sgnH基因和9个未知功能的orf基因有差异外，S. gilvosporeus F607基因簇中其他纳他霉素生物合成基因及其排列顺序与已知的纳他霉素基因簇高度一致。【结论】分析了S. gilvosporeus全基因组信息，预测了S. gilvosporeus F607中纳他霉素生物合成的途径，为从基因组层面上解析S. gilvosporeus F607菌株高产纳他霉素的内在原因提供了基础数据，为揭示纳他霉素高产的机理及工业化生产和未来新药的发现奠定了良好的基础。

Abstract:

[Background] Natamycin is a natural, broad-spectrum and efficient polyene macrolide antifungal antibiotic. Streptomyces gilvosporeus is an important natamycin-producing bacterium. However, the genome sequence analysis of S. gilvosporeus has not been reported until now, limiting studies on the biosynthesis and regulation of natamycin and other secondary metabolites in S. gilvosporeus. [Objective] The genomic sequence information of the S. gilvosporeus F607 (a natamycin high-producing strain) was analyzed to explore the genetic resources of secondary metabolite genes and lay a foundation for further study on the mechanisms of high producing and regulation of natamycin biosynthesis. [Methods] The genome sequence of F607 was analyzed with softwares to predict genes, to annotate function of genes, to analyze phylogenetic tree and colinear analysis, and to predict the secondary metabolite synthetic gene cluster; The differences of natamycin biosynthetic gene clusters in different strains were analyzed and compared through annotating analysis of natamycin biosynthetic gene clusters; the biosynthetic pathway of natamycin was analyzed and predicted according to gene function. [Results] The complete genome sequence of F607 is 8 482 298 bp ((G+C)mol%, 70.95%). 5 062, 4 428, 5 063 genes were respectively predicted in COG, GO and KEGG databases. The antiSMASH software predicted that there are 29 secondary metabolite biosynthetic gene clusters in F607 genome. The homology of natamycin biosynthetic gene cluster in F607 shared 81% and 77% with that in S. natalensis and S. chattanoogensis respectively. Although there were differences among 2 regulatory genes (sngT, sgnH) and 9 unknown function genes (orf1?9), the analysis of natamycin biosynthetic gene clusters in different strains indicated that the other genes and their arrangement in natamycin biosynthetic gene cluster are highly conserved. [Conclusion] In this study, the complete genome sequence of strain F607 was first analyzed and the biosynthetic pathway of natamycin of F607 was predicted. This study provides basic data for analysis of the molecular mechanism of high-yield natamycin in S. gilvosporeus F607, and aids in the development of useful strategies for revealing the mechanism of high yield of natamycin, improving industrial strains and innovating drug discovery.