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首页> 外文期刊>Catalysis science & technology >Nitrile reductase as a biocatalyst: opportunities and challenges
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Nitrile reductase as a biocatalyst: opportunities and challenges

机译：硝酸还原酶作为生物催化剂：机遇和挑战

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摘要

Nitrile-containing compounds are widely manufactured and extensively used in the chemical and pharmaceutical industries as synthetic intermediates or precursors. Nitrile hydratase and nitrilase have been successfully developed as biocatalysts for the production of amides and carboxylic acids from nitrile precursors. The discovery of a family of nitrile reductases that catalyse the reduction of nitrile to amine raised the hope of developing environmentally sustainable nitrile-reducing biocatalysts to replace metal hydride catalysts. However, ten years after the discovery of the QueF nitrile reductases, little progress has been made towards the development of nitrile reductase biocatalysts with altered or broadened substrate specificity. In this article, we analyse and review the structure and catalytic mechanism of QueF nitrile reductases and other structurally related T-fold family enzymes. We argue that the poor evolvability of the T-fold enzymes and the kinetically sluggish reaction catalysed by QueFs pose formidable challenges for developing this family of enzymes into practically useful biocatalysts. The challenges do not seem to be mitigated by current' computational design or directed-evolution methods. Searching for another family of nitrile reductases or engineering a more evolvable protein scaffold to support the nitrile-reducing chemistry may be a more viable strategy to develop a nitrile reductase biocatalyst despite another set of foreseeable challenges.
机译：含氮化合物在化学和制药行业中广泛生产和广泛用作合成中间体或前体。硝酸水合物和硝酸酶已成功开发为氮氮前体酰胺和羧酸的生物催化剂。发现了一个硝酸还原酶的家族，该家族催化氮的还原为胺促进了胺的希望，这使人们希望开发环境可持续的硝酸氮化生物催化剂，以替代金属氢化物催化剂。然而，在发现Quef硝酸还原酶十年后，几乎没有取得变化或扩大底物特异性的硝酸还原酶生物催化剂的发展。在本文中，我们分析和回顾了Quef氮还原酶和其他结构相关的T折家酶的结构和催化机制。我们认为，T折酶的不良可发展性和Quefs催化的动力学缓慢反应构成了将这种酶家族开发为实际上有用的生物催化剂的巨大挑战。当前的计算设计或定向进化方法似乎并没有缓解挑战。寻找另一家硝酸还原酶或工程性的蛋白质支架来支持降低硝酸盐的蛋白质支架，尽管还有另一系列可预见的挑战，但仍有更可行的策略来开发硝酸还原酶生物催化剂。

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