瑞士洛桑联邦理工学院胡喜乐团队发现了半合成[Mn]‐氢化酶中金属‐配体协同催化的多样性。 相关研究成果于2021年2月26日发表于国际顶尖学术期刊《德国应用化学》。

人工酶已发展成为新型的生物催化剂和酶作用机理的有效探针。然而，人工酶很少通过天然酶反应的新机制进行操作。

该文中，研究人员描述了用一系列Mn（I）络合物重构[Mn]-氢化酶。这些配合物被特别设计为具有可能参与金属-配体协同催化的内碱或前碱，或者没有内碱或前碱。只有具有内碱或前碱的Mn（I）络合物对H2活化反应具有活性。只有[Mn]-氢化酶结合了这种复合物，才对氢化酶反应具有活性。

这些结果证实了金属-配体相互作用对单独的Mn（I）络合物和[Mn]氢化酶激活H2的重要作用。由于Mn（I）络合物中内碱基或前碱基的性质和位置，两种活性[Mn]氢化酶中的金属-配体相互作用模式与天然[Fe]氢化酶不同。其中一种[Mn]-氢化酶在所有已知的半合成[Mn]-和[Fe]-氢化酶中表现出最高的比活性。

该工作证明了使用合成复合物重组活性人工氢化酶大大不同于天然活性位点。该策略可用于开发新型生物催化剂。

附：英文原文

Title: Diversifying metal‐ligand cooperative catalysis in semi‐synthetic [Mn]‐hydrogenases

Author: Huijie Pan, Gangfeng Huang, Matthew Wodrich, Farzaneh Fadaei Tirani, Kenichi Ataka, Seigo Shima, Xile Hu

Issue&Volume: 2021-02-26

Abstract: Artificial enzymes have been developed into novel biocatalysts and useful probes of enzyme mechanisms. However, artificial enzymes rarely operate by a new‐to‐nature mechanism for the native enzyme reactions. Here we describe the reconstitution of [Mn]‐hydrogenases using a series of Mn(I) complexes. These complexes are specifically designed to either have an internal base or pro‐base that may participate in metal‐ligand cooperative catalysis, or have no internal base or pro‐base. Only Mn(I) complexes with an internal base or pro‐base are active for H2 activation. Only [Mn]‐hydrogenases incorporating such complexes are active for hydrogenase reactions. These results confirm the essential role of metal‐ligand cooperation for H2 activation by both the Mn(I) complexes alone and by [Mn]‐hydrogenases. Due to the nature and position of the internal base or pro‐base in the Mn(I) complexes, the mode of metal‐ligand cooperation in two active [Mn]‐hydrogenases is different from that of the native [Fe]‐hydrogenase. One such [Mn]‐hydrogenase exhibits the highest specific activity among all known semi‐synthetic [Mn]‐ and [Fe]‐hydrogenases. This work demonstrates the reconstitution of active artificial hydrogenases using synthetic complexes that differ substantially from the native active site. This strategy might be applied to develop new biocatalysts.

DOI: 10.1002/anie.202100443

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202100443