Enzymatic synthesis of polymeric materials is a powerful approach to make these processes greener, more economical, and safer for scale-up. Herein, we characterized new variants of the hyperthermophilic carboxylesterase from the archaeon Archaeoglobus fulgidus with quantum mechanics/molecular mechanics molecular dynamics simulations. The designed variants were expressed and tested for the synthesis of poly(ε-caprolactone) and triblock poly(ε-caprolactone)–poly(ethylene glycol), two important biomaterials. The reactant complexes of the best variants formed stronger hydrogen bonds with the nucleophilic oxygen and the subsequent tetrahedral intermediates formed stronger hydrogen bonds with the leaving lactone oxygen, reflecting the best active site preorganization for stabilization of the two consecutive transition states that involve the same active site machinery. Our findings set the underpinning ground to redesign other enzymes for polyesterification reactions.

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用于合成生物可吸收聚酯的酶变体的开发

聚合材料的酶促合成是使这些工艺更环保、更经济、更安全的放大方法。在这里，我们表征了来自古生菌Archaeoglobus fulgidus的超嗜热羧酸酯酶的新变体与量子力学/分子力学分子动力学模拟。设计的变体被表达并测试了聚（ε-己内酯）和三嵌​​段聚（ε-己内酯）-聚（乙二醇）的合成，这两种重要的生物材料。最佳变体的反应物配合物与亲核氧形成更强的氢键，随后的四面体中间体与离开的内酯氧形成更强的氢键，反映了用于稳定涉及相同活性位点的两个连续过渡态的最佳活性位点预组织机械。我们的研究结果为重新设计用于聚酯化反应的其他酶奠定了基础。