论文标题
链霉菌代谢的功能和进化基因组学
Functional and evolutionary genomics of the Streptomyces metabolism
论文作者
论文摘要
该论点集中在研究链霉菌代谢库的演变上，链霉菌作为生物活性天然产物（NPS）的熟练生产者闻名。我工作的主要目标是为理解NP生物合成途径进化背后的进化机制做出贡献。具体而言，生物信息学方法的发展有助于从放线菌基因组序列发现新的NP生物合成途径，重点是链霉菌属成员。我使用比较和功能基因组学角度开发了这种方法。我的研究表明，中央代谢酶以静脉细菌的特异性方式扩展，并已广泛招募NP的生物合成。基于这些观察结果，我开发了发动机，这是微生物基因组中新型生物合成途径识别的生物信息学管道。已经预测了在肌动杆菌的不同成员中，已经预测了使用蒸发的几种新的NP生物合成途径，包括模型有机体S. lividans 66。为了测试这种方法，获得了该模型菌株的基因组序列，并且其分析导致发现了一种前所未有的肽键形成系统，并发现了一个生物量的态度。此外，这项工作还导致鉴定在链霉菌糖酵解途径中保守的代谢节点上的扩张。这些膨胀发生在链霉菌的辐射之前，与它们产生NP的能力的演变同时。实验分析表明，该节点演变为介导NP代谢中心之间的相互作用。
This thesis is focused in the study of the evolution of the metabolic repertoire of Streptomyces, which are renowned as proficient producers of bioactive Natural Products (NPs). The main goal of my work was to contribute into the understanding of the evolutionary mechanisms behind the evolution of NP biosynthetic pathways. Specifically, the development of a bioinformatic method that helps into the discovery of new NP biosynthetic pathways from actinobacterial genome sequences with emphasis on members of the genus Streptomyces. I developed this method using a comparative and functional genomics perspective. My studies indicate that central metabolic enzymes were expanded in a genus-specific manner in Actinobacteria, and that they have been extensively recruited for the biosynthesis of NPs. Based in these observations, I developed EvoMining, a bioinformatic pipeline for the identificatoon of novel biosynthetic pathways in microbial genomes. Using EvoMining several new NP biosynthetic pathways have been predicted in different members of the phylum Actinobacteria, including the model organism S. lividans 66. To test this approach, the genome sequence of this model strain was obtained, and its analysis led to the discovery of an unprecedented system for peptide bond formation, as well as a biosynthetic pathway for an arsenic-containing metabolite. Moreover, this work also led to the identification of expansions on a conserved metabolic node in the glycolytic pathway of Streptomyces. These expansions occurred before the radiation of Streptomyces and are concomitant with the evolution of their capability to produce NPs. Experimental analyses indicate that this node evolved to mediate the interplay between central an NP metabolism.
