Protein cost minimization promotes the emergence of coenzyme redundancy.
Protein cost minimization promotes the emergence of coenzyme redundancy.
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DOI：
10.1073/pnas.2110787119
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发表时间：
2022-04-05
影响因子：
11.1
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中科院分区：
文献类型：
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代谢依赖于一小类分子（辅酶），它们是关键化学基团和电子的通用供体和受体。尽管代谢网络关键地依赖于结构冗余的辅酶[例如，NAD（H）和NADP（H）]与不同的酶相关，导致这种冗余出现的标准仍然知之甚少。我们的建模和结构和序列分析的组合表明，辅酶冗余可能不是必不可少的代谢，而是可以构成一个进化的策略，促进有效利用酶时，生化反应接近平衡。我们的工作表明，早期代谢可能是在辅酶较少的情况下进行的，而对代谢效率的适应可能推动了生命系统中辅酶多样性的增加。辅酶在整个细胞代谢中分布各种化学部分，参与组（例如，磷酸和酰基）和电子转移。对于需要特定资源的受体或供体的各种反应，通常存在分子的简并集合[例如，NAD（H）和NADP（H）]执行类似功能。虽然各种辅酶系统的生理作用已经很好地建立，但还不清楚是什么选择压力驱动了辅酶冗余的出现。在这里，我们使用全基因组代谢建模方法来分解大肠杆菌代谢网络中驱动NAD（H）或NADP（H）酶特异性的选择压力。我们发现，很少有酶被限制使用单一的辅酶，原则上只依赖于NAD（H）的代谢网络是可行的。然而，结构和序列分析揭示了保留对NAD（H）或NADP（H）的选择性的残基的广泛保守性，这表明额外的力可能形成特异性。使用一个模型占氧化还原酶表达的成本，我们发现，辅酶冗余普遍减少催化辅酶偶联反应所需的蛋白质的最小量，诱导个别反应强烈倾向于一个辅酶超过另一个反应时，反应接近热力学平衡。我们提出蛋白质最小化一般促进辅酶冗余，并且通常认为辅酶存在于单个池中（例如，辅酶A [CoA]）可以以一种以上的形式存在（例如，脱磷酸-CoA）。
Metabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes [e.g., NAD(H) and NADP(H)] associated with different enzymes, the criteria that led to the emergence of this redundancy remain poorly understood. Our combination of modeling and structural and sequence analysis indicates that coenzyme redundancy may not be essential for metabolism but could rather constitute an evolved strategy promoting efficient usage of enzymes when biochemical reactions are near equilibrium. Our work suggests that early metabolism may have operated with fewer coenzymes and that adaptation for metabolic efficiency may have driven the rise of coenzyme diversity in living systems. Coenzymes distribute a variety of chemical moieties throughout cellular metabolism, participating in group (e.g., phosphate and acyl) and electron transfer. For a variety of reactions requiring acceptors or donors of specific resources, there often exist degenerate sets of molecules [e.g., NAD(H) and NADP(H)] that carry out similar functions. Although the physiological roles of various coenzyme systems are well established, it is unclear what selective pressures may have driven the emergence of coenzyme redundancy. Here, we use genome-wide metabolic modeling approaches to decompose the selective pressures driving enzymatic specificity for either NAD(H) or NADP(H) in the metabolic network of Escherichia coli. We found that few enzymes are thermodynamically constrained to using a single coenzyme, and in principle a metabolic network relying on only NAD(H) is feasible. However, structural and sequence analyses revealed widespread conservation of residues that retain selectivity for either NAD(H) or NADP(H), suggesting that additional forces may shape specificity. Using a model accounting for the cost of oxidoreductase enzyme expression, we found that coenzyme redundancy universally reduces the minimal amount of protein required to catalyze coenzyme-coupled reactions, inducing individual reactions to strongly prefer one coenzyme over another when reactions are near thermodynamic equilibrium. We propose that protein minimization generically promotes coenzyme redundancy and that coenzymes typically thought to exist in a single pool (e.g., coenzyme A [CoA]) may exist in more than one form (e.g., dephospho-CoA).
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影响因子：
4.7
作者：
Cahn JK;Werlang CA;Baumschlager A;Brinkmann-Chen S;Mayo SL;Arnold FH
通讯作者：
Arnold FH
DOI：
10.1073/pnas.2005642117
发表时间：
2020-12-29
影响因子：
11.1
作者：
Jinich A;Sanchez-Lengeling B;Ren H;Goldford JE;Noor E;Sanders JN;Segrè D;Aspuru-Guzik A
通讯作者：
Aspuru-Guzik A
DOI：
10.1098/rspb.2016.1536
发表时间：
2016-09-28
影响因子：
4.7
作者：
Hosseini, Sayed-Rzgar;Martin, Olivier C.;Wagner, Andreas
通讯作者：
Wagner, Andreas
影响因子：
4.3
作者：
Jinich A;Flamholz A;Ren H;Kim SJ;Sanchez-Lengeling B;Cotton CAR;Noor E;Aspuru-Guzik A;Bar-Even A
通讯作者：
Bar-Even A
影响因子：
3.7
作者：
Armingol, Erick;Tobar, Eduardo;Cabrera, Ricardo
通讯作者：
Cabrera, Ricardo