Bazurto Jannell V, Farley Kristen R, Downs Diana M
Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Department of Microbiology, University of Georgia, Athens, Georgia, USA
mBio. 2016 Jan 5;7(1):e01840-15. doi: 10.1128/mBio.01840-15.
Metabolism consists of biochemical reactions that are combined to generate a robust metabolic network that can respond to perturbations and also adapt to changing environmental conditions. Escherichia coli and Salmonella enterica are closely related enterobacteria that share metabolic components, pathway structures, and regulatory strategies. The synthesis of thiamine in S. enterica has been used to define a node of the metabolic network by analyzing alternative inputs to thiamine synthesis from diverse metabolic pathways. To assess the conservation of metabolic networks in organisms with highly conserved components, metabolic contributions to thiamine synthesis in E. coli were investigated. Unexpectedly, we found that, unlike S. enterica, E. coli does not use the phosphoribosylpyrophosphate (PRPP) amidotransferase (PurF) as the primary enzyme for synthesis of phosphoribosylamine (PRA). In fact, our data showed that up to 50% of the PRA used by E. coli to make thiamine requires the activities of threonine dehydratase (IlvA) and anthranilate synthase component II (TrpD). Significantly, the IlvA- and TrpD-dependent pathway to PRA functions in S. enterica only in the absence of a functional reactive intermediate deaminase (RidA) enzyme, bringing into focus how these closely related bacteria have distinct metabolic networks.
In most bacteria, including Salmonella strains and Escherichia coli, synthesis of the pyrimidine moiety of the essential coenzyme, thiamine pyrophosphate (TPP), shares enzymes with the purine biosynthetic pathway. Phosphoribosylpyrophosphate amidotransferase, encoded by the purF gene, generates phosphoribosylamine (PRA) and is considered the first enzyme in the biosynthesis of purines and the pyrimidine moiety of TPP. We show here that, unlike Salmonella, E. coli synthesizes significant thiamine from PRA derived from threonine using enzymes from the isoleucine and tryptophan biosynthetic pathways. These data show that two closely related organisms can have distinct metabolic network structures despite having similar enzyme components, thus emphasizing caveats associated with predicting metabolic potential from genome content.
新陈代谢由生化反应组成，这些反应相互结合形成一个强大的代谢网络，该网络能够对扰动做出反应，并适应不断变化的环境条件。大肠杆菌和肠炎沙门氏菌是密切相关的肠道细菌，它们共享代谢成分、途径结构和调控策略。通过分析来自不同代谢途径的硫胺素合成的替代输入，肠炎沙门氏菌中硫胺素的合成已被用于定义代谢网络的一个节点。为了评估具有高度保守成分的生物体中代谢网络的保守性，研究了大肠杆菌中硫胺素合成的代谢贡献。出乎意料的是，我们发现，与肠炎沙门氏菌不同，大肠杆菌不使用磷酸核糖焦磷酸（PRPP）酰胺转移酶（PurF）作为合成磷酸核糖胺（PRA）的主要酶。事实上，我们的数据表明，大肠杆菌用于合成硫胺素的PRA中，高达50%需要苏氨酸脱水酶（IlvA）和邻氨基苯甲酸合酶组分II（TrpD）的活性。值得注意的是，依赖IlvA和TrpD的PRA途径仅在缺乏功能性反应性中间脱氨酶（RidA）酶的肠炎沙门氏菌中起作用，这凸显了这些密切相关的细菌如何具有不同的代谢网络。
在大多数细菌中，包括沙门氏菌菌株和大肠杆菌，必需辅酶硫胺素焦磷酸（TPP）的嘧啶部分的合成与嘌呤生物合成途径共享酶。由purF基因编码的磷酸核糖焦磷酸酰胺转移酶生成磷酸核糖胺（PRA），被认为是嘌呤和TPP嘧啶部分生物合成中的第一种酶。我们在此表明，与沙门氏菌不同，大肠杆菌使用来自异亮氨酸和色氨酸生物合成途径的酶，从源自苏氨酸的PRA中合成大量硫胺素。这些数据表明，尽管两种密切相关的生物体具有相似的酶成分，但它们可以具有不同的代谢网络结构，从而强调了从基因组内容预测代谢潜力相关的注意事项。
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