How to Recruit a Promiscuous Enzyme to Serve a New Function.
How to Recruit a Promiscuous Enzyme to Serve a New Function.
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DOI：
10.1021/acs.biochem.2c00249
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发表时间：
2023-01-17
期刊：
影响因子：
2.9
通讯作者：
Widney, Karl A.
中科院分区：
文献类型：
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作者：
Copley, Shelley D.;Newton, Matilda S.;Widney, Karl A.
当遗传或环境变化使得催化新反应对健康甚至生存很重要时，可以招募混杂的酶来发挥新功能。随后，基因复制和分化可以导致高效且专门的新酶的进化。每个生物体都可能具有数千种混杂的酶活性，这些酶活性提供了巨大的催化潜力。然而，这种潜力的大部分可能无法发挥。我们编制了 108 种酶催化的混杂反应的动力学参数。 kcat/KM 的中值非常适中，为 31 M−1s−1。根据大肠杆菌代谢途径的通量，我们估计许多（如果不是大多数）混杂的活动效率太低，无法影响健康。然而，突变可以通过增加酶表达、改善 kcat/KM 或改变混杂和天然底物以及变构调节剂的浓度来提高混杂活性不足的水平。特别是在大型细菌群体中，随机突变可能为招募甚至低效的混杂活动提供可行的途径。
Promiscuous enzymes can be recruited to serve new functions when a genetic or environmental change makes catalysis of a novel reaction important for fitness or even survival. Subsequently, gene duplication and divergence can lead to evolution of an efficient and specialized new enzyme. Every organism likely has thousands of promiscuous enzyme activities that provide a vast reservoir of catalytic potential. However, much of this potential may not be accessible. We compiled kinetic parameters for promiscuous reactions catalyzed by 108 enzymes. The median value of kcat/KM is a very modest 31 M−1s−1. Based upon the fluxes through metabolic pathways in E. coli, we estimate that many, if not most, promiscuous activities are too inefficient to impact fitness. However, mutations can elevate the level of an insufficient promiscuous activity by increasing enzyme expression, improving kcat/KM, or altering concentrations of the promiscuous and native substrates and allosteric regulators. Particularly in large bacterial populations, stochastic mutations may provide a viable pathway for recruitment of even inefficient promiscuous activities.
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影响因子：
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作者：
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