Department of Bioengineering, University of California San Diego, La Jolla, CA 92093-0412, USA.
Science. 2012 Aug 31;337(6098):1101-4. doi: 10.1126/science.1216861.
Enzymes are thought to have evolved highly specific catalytic activities from promiscuous ancestral proteins. By analyzing a genome-scale model of Escherichia coli metabolism, we found that 37% of its enzymes act on a variety of substrates and catalyze 65% of the known metabolic reactions. However, it is not apparent why these generalist enzymes remain. Here, we show that there are marked differences between generalist enzymes and specialist enzymes, known to catalyze a single chemical reaction on one particular substrate in vivo. Specialist enzymes (i) are frequently essential, (ii) maintain higher metabolic flux, and (iii) require more regulation of enzyme activity to control metabolic flux in dynamic environments than do generalist enzymes. Furthermore, these properties are conserved in Archaea and Eukarya. Thus, the metabolic network context and environmental conditions influence enzyme evolution toward high specificity.
酶被认为是从杂乱无章的祖先蛋白质中进化出高度特异的催化活性。通过分析大肠杆菌代谢的基因组规模模型，我们发现其 37%的酶作用于多种底物，并催化 65%的已知代谢反应。然而，这些通用酶为什么仍然存在并不明显。在这里，我们表明，通用酶和专门酶之间存在明显的差异，专门酶已知在体内催化一种特定底物上的单一化学反应。专门酶 (i) 经常是必需的，(ii) 保持更高的代谢通量，(iii) 需要更多的酶活性调节来控制动态环境中的代谢通量，而通用酶则不需要。此外，这些特性在古菌和真核生物中是保守的。因此，代谢网络的背景和环境条件影响着酶向高特异性的进化。
