Evolution trains a from-scratch catalyst Metal-bound peptides can catalyze simple reactions such as ester hydrolysis and may have been the starting point for the evolution of modern enzymes. Studer et al. selected progressively more-proficient variants of a small protein derived from a computationally designed zinc-binding peptide. The resulting enzyme could perform the trained reaction at rates typical for naturally evolved enzymes and serendipitously developed a strong preference for a single enantiomer of the substrate. A structure of the final catalyst highlights how small, progressive changes can remodel both catalytic residues and protein architecture in unpredictable ways. Science, this issue p. 1285 A metal-binding peptide becomes a potent catalyst for ester hydrolysis. Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (kcat/KM ~ 106 M−1 s−1). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.

中文翻译：

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从短肽进化出高活性和对映特异性金属酶

进化训练从头开始的催化剂金属结合肽可以催化简单的反应，如酯水解，可能是现代酶进化的起点。斯图德等人。从计算设计的锌结合肽衍生的小蛋白质的逐渐更熟练的变体。由此产生的酶可以以自然进化酶的典型速率进行训练反应，并且意外地对底物的单一对映异构体产生了强烈的偏好。最终催化剂的结构突出了微小的渐进变化可以以不可预测的方式重塑催化残基和蛋白质结构。科学，这个问题 p。1285 金属结合肽成为酯水解的有效催化剂。现代蛋白质中的原始序列特征意味着可以追溯到简单肽的祖先起源。虽然短肽很少采用独特的折叠，但金属离子可能在早期进化中将它们组装成更高阶的结构并赋予有用的化学反应性。回顾这样的生物遗传场景，我们结合设计和实验室进化，将锌结合肽转化为能够以严格的对映特异性和高催化效率（kcat/KM ~ 106 M-1 s-1）加速酯裂解的球状酶。天然肽支架中结构和功能的同时优化不仅说明了从遥远的过去到现在的合理的酶进化途径，而且为酶设计和工程提供了令人兴奋的未来机会。