Comparative genomic analysis of dha regulon and related genes for anaerobic glycerol metabolism in bacteria
Comparative genomic analysis of dha regulon and related genes for anaerobic glycerol metabolism in bacteria
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DOI：
10.1021/bp025739m
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发表时间：
2003-03-01
影响因子：
2.9
通讯作者：
Zeng, AP
中科院分区：
文献类型：
--
作者：
Sun, JB;van den Heuvel, J;Zeng, AP
细菌的二羟基丙酮 (dha) 调节子编码甘油无氧代谢的基因。在这项工作中，基因组数据用于在计算机上分析和比较不同生物体中的 dha 调节子和相关基因的基因组织、序列相似性和可能的功能。数据库搜索显示，在迄今为止基因组已测序的生物中，只有两种，即肺炎克雷伯菌 MGH 78578 和产气荚膜梭菌，含有完整的 dha 调节子，该调节子具有所有已知的酶。这两种生物体的 dha 调节子的成分及其组织彼此之间存在很大差异，也与之前在弗氏柠檬酸杆菌、巴氏梭菌和丁酸梭菌中部分测序的 dha 调节子存在很大差异。与所有其他生物体不同，产气荚膜梭菌厌氧甘油代谢的氧化和还原途径的基因位于染色体上的两个独立的组织单位中。对具有相似功能的基因推导的蛋白质序列进行比较表明，肺炎克雷伯菌和弗氏衣原体的dha调节子成分具有较高的相似性(80-95%)，但与梭状芽胞杆菌属的相似性较低(30-80%)。有趣的是，梭菌属物种的 dha 基因之间的蛋白质序列相似性在许多情况下甚至低于梭菌属物种与肺炎克雷伯菌或弗氏梭菌之间的蛋白质序列相似性，表明所研究的梭菌属物种中存在两种不同类型的 dha 调节子。 dha 调节子的计算机重建和比较揭示了所研究的微生物中的几个新基因。特别是，除了已知的 ATP 依赖性 dha 激酶之外，还针对肺炎克雷伯菌鉴定并通过实验证实了一种磷酸烯醇丙酮酸依赖性的新型 dha 激酶。这一发现为肺炎克雷伯菌甘油代谢的调节提供了新的见解，并解释了一些迄今尚未充分理解的实验观察结果。
The dihydroxyacetone (dha) regulon of bacteria encodes genes for the anaerobic metabolism of glycerol. In this work, genomic data are used to analyze and compare the dha regulon and related genes in different organisms in silico with respect to gene organization, sequence similarity, and possible functions. Database searches showed that among the organisms, the genomes of which have been sequenced so far, only two, i.e., Klebsiella pneumoniae MGH 78578 and Clostridium perfringens contain a complete dha regulon bearing all known enzymes. The components and their organization in the dha regulon of these two organisms differ considerably from each other and also from the previously partially sequenced dha regulons in Citrobacter freundii, Clostridium pasteurianum, and Clostridium butyricum. Unlike all of the other organisms, genes for the oxidative and reductive pathways of anaerobic glycerol metabolism in C. perfringens are located in two separate organization units on the chromosome. Comparisons of deduced protein sequences of genes with similar functions showed that the dha regulon components in K. pneumoniae and C. freundii have high similarities (80-95%) but lower similarities to those of the Clostridium species (30-80%). Interestingly, the protein sequence similarities among the dha genes of the Clostridium species are in many cases even lower than those between the Clostridium species and K pneumoniae or C. freundii, suggesting two different types of dha regulon in the Clostridium species studied. The in silico reconstruction and comparison of dha regulons revealed several new genes in the microorganisms studied. In particular, a novel dha kinase that is phosphoenolpyruvate-dependent is identified and experimentally confirmed for K pneumoniae in addition to the known ATP-dependent dha kinase. This finding gives new insights into the regulation of glycerol metabolism in K. pneumoniae and explains some hitherto not well understood experimental observations.