Enzyme engineering: reaching the maximal catalytic efficiency peak
Enzyme engineering: reaching the maximal catalytic efficiency peak
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DOI：
10.1016/j.sbi.2017.09.002
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发表时间：
2017-12-01
影响因子：
6.8
通讯作者：
Tawfik, Dan S.
中科院分区：
文献类型：
--
作者：
Goldsmith, Moshe;Tawfik, Dan S.
对高效酶的实际需求在酶工程中提出了新的挑战，特别是需要将催化周转率（k（cat））或效率（k（cat）/K-M）提高几个数量级。然而，优化催化需要通过复杂和崎岖的健身景观导航，优化轨迹往往导致强烈的收益递减和死胡同。当在文库筛选或选择中没有观察到进一步的改进时，仍然不清楚是否已经达到酶的最大催化效率（催化“适应性峰”）;或者可能存在可以产生额外改进的替代突变组合。在这里，我们讨论了催化优化过程的基本方面，并提供了克服优化高原的实用解决方案。
The practical need for highly efficient enzymes presents new challenges in enzyme engineering, in particular, the need to improve catalytic turnover (k(cat)) or efficiency (k(cat)/K-M) by several orders of magnitude. However, optimizing catalysis demands navigation through complex and rugged fitness landscapes, with optimization trajectories often leading to strong diminishing returns and dead-ends. When no further improvements are observed in library screens or selections, it remains unclear whether the maximal catalytic efficiency of the enzyme (the catalytic 'fitness peak') has been reached; or perhaps, an alternative combination of mutations exists that could yield additional improvements. Here, we discuss fundamental aspects of the process of catalytic optimization, and offer practical solutions with respect to overcoming optimization plateaus.