EVOLUTION OF METABOLISM: MICROBIAL GENOMES

新陈代谢的进化：微生物基因组

• 批准号: 6282412
• 负责人: CHRISTIAN FORST
• 金额: $ 9.25万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6282412
• 关键词: bacteria; biomedical resource; genetics; genome; microorganism; structural biology; technology /technique

The abundance of genomic information by completely sequenced microbial genomes provides a starting point for new insights in the multi-level organization of organisms and their evolution*. We take the next step, away from annotating genes by functions of expressed proteins, towards a more comprehensive description of metabolic pathways of proteins acting as enzymes processing substrates [64]. By comparing pathogenic microbes with free living organisms the pathogenicity can be related to functions which are missing in autotrophs. H. influencae and E. coli are a well known example for such relationships. Similar results can be reported for free living B. subtilis and pathogenic Streptococci. This study aids in drug design and disease treatment by interfering with host-interaction factors and pathways of pathogens. We also pursue the development of methods to construct phylogenies between organisms on the level of metabolic pathways. By a graph-theoretical approach combined with sequence information, pathways of different organisms are related to each other. First results have been obtained by applying this method on pathways related to electron transfer. This suggests the chimeric origin of archaea and thus an early evolution of such pathways [65]. On sequence level and gene cluster organization a closer relationship to bacteria than to eucarya can be reported. These accomplishments open the door for reconstructing the minimal set of genes, regulatory and metabolic pathways of the universal ancestor of all three kingdoms, archaea, bacteria and eucarya.

完整测序的丰富基因组信息 微生物基因组为新见解提供了起点 生物体的多层次组织及其进化*。 我们采取 下一步，不再通过表达的功能来注释基因 蛋白质，以更全面地描述代谢 作为酶处理底物的蛋白质的途径[64]。 经过 将病原微生物与自由生物体进行比较 致病性可能与缺失的功能有关 自养生物。 流感嗜血杆菌和大肠杆菌是众所周知的例子 这样的关系。 自由生活也有类似的结果 枯草芽孢杆菌和致病性链球菌。 这项研究有助于药物 通过干扰宿主相互作用进行设计和疾病治疗 病原体的因素和途径。 我们还追求发展 在生物体水平上构建系统发育的方法 代谢途径。 通过图论方法结合 序列信息，不同生物体的途径相关 彼此。 应用该方法已获得初步结果 与电子转移相关的途径。 这表明嵌合 古细菌的起源以及此类途径的早期进化[65]。 在序列水平上与基因簇组织有更密切的关系 据报道，对细菌的影响要大于对真核生物的影响。 这些成就 打开重建最小基因组、调控基因组的大门 以及这三个物种的共同祖先的代谢途径 界、古细菌、细菌和真核生物。