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金黄色葡萄球菌生理生长限制:基于蛋白质组学和外部代谢物数据的通量计算的见解。

Staphylococcus aureus physiological growth limitations: insights from flux calculations built on proteomics and external metabolite data.

机构信息

Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany.

出版信息

Proteomics. 2011 May;11(10):1915-35. doi: 10.1002/pmic.201000151. Epub 2011 Apr 7.

DOI:10.1002/pmic.201000151
PMID:21472852
Abstract

Comparing proteomics and metabolomics allows insights into Staphylococcus aureus physiological growth. We update genome and proteome information and deliver strain-specific metabolic models for three S. aureus strains (COL, N315, and Newman). We find a number of differences in metabolism and enzymes. Growth experiments (glucose or combined with oxygen limitation) were conducted to measure external metabolites. Fluxes of the central metabolism were calculated from these data with low error. In exponential phase, glycolysis is active and amino acids are used for growth. In later phases, dehydroquinate synthetase is suppressed and acetate metabolism starts. There are strain-specific differences for these phases. A time series of 2-D gel protein expression data on COL strain delivered a second data set (glucose limitation) on which fluxes were calculated. The comparison with the metabolite-predicted fluxes shows, in general, good correlation. Outliers point to different regulated enzymes for S. aureus COL under these limitations. In exponential growth, there is lower activity for some enzymes in upper glycolysis and pentose phosphate pathway and stronger activity for some in lower glycolysis. In transition phase, aspartate kinase is expressed to meet amino acid requirements and in later phases there is high expression of glyceraldehyde-3-phosphate dehydrogenase and lysine synthetase. Central metabolite fluxes and protein expression of their enzymes correlate in S. aureus.

摘要

比较蛋白质组学和代谢组学可以深入了解金黄色葡萄球菌的生理生长。我们更新了三个金黄色葡萄球菌菌株(COL、N315 和 Newman)的基因组和蛋白质组信息,并提供了菌株特异性的代谢模型。我们发现了代谢和酶的许多差异。进行了生长实验(葡萄糖或与氧气限制相结合)以测量外部代谢物。从这些数据中计算出中心代谢物的通量,误差很小。在指数生长期,糖酵解活跃,氨基酸用于生长。在后期,脱氢奎宁酸合酶被抑制,乙酸代谢开始。这些阶段存在菌株特异性差异。对 COL 菌株的 2-D 凝胶蛋白表达数据进行时间序列分析,提供了第二个数据集(葡萄糖限制),并在该数据集上计算了通量。与代谢物预测通量的比较表明,一般来说,相关性很好。异常值表明,在这些限制下,金黄色葡萄球菌 COL 的调节酶不同。在指数生长期间,在上糖酵解和戊糖磷酸途径中一些酶的活性较低,而在下糖酵解中一些酶的活性较强。在过渡阶段,天冬氨酸激酶的表达满足了氨基酸的需求,而在后期,甘油醛-3-磷酸脱氢酶和赖氨酸合成酶的表达水平很高。金黄色葡萄球菌中,中心代谢物通量和酶的蛋白质表达相关。

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