英国剑桥大学Paul D. Barker团队通过钌有机金属辅助因子前体和天然蛋白质支架之间的受控配体交换产生人工金属酶催化转移氢化。相关研究成果于2021年2月22日发表在国际知名学术期刊《德国应用化学》。
许多天然金属酶由蛋白质和生物合成的复合物组装而成，通过改变金属配位来产生高效的催化剂。
该文中，研究人员采用同样的策略，通过配体交换来产生人工金属酶揭示催化活性。通过系统地测试旨在促进取代功能化联吡啶Ru（II）（η6-芳烃）（联吡啶）配合物，研究人员开发了一种快速而稳健的程序，通过蛋白质中的配体交换产生新的酶，而蛋白质尚未进化到结合这种复合物。由此产生的金属辅因子形成肽配位键，但也保留了非生物配体。串联质谱和19F核磁共振波谱表征了有机金属辅因子，并鉴定了蛋白质衍生配体。
通过在4螺旋束中引入钌辅助因子，生成了转移氢化反应的催化剂，与溶液中相应的小分子反应相比，转移氢化催化剂的速率提高了35倍。
附：英文原文
Title: Controlled Ligand Exchange Between Ruthenium Organometallic Cofactor Precursors and a Naïve Protein Scaffold Generates Artificial Metalloenzymes Catalysing Transfer Hydrogenation
Author: George Biggs, Oskar James Klein, Sarah Maslen, J. Mark Skehel, Trevor J. Rutherford, Stefan M.V. Freund, Florian Hollfelder, Sally R. Boss, Paul D. Barker
Issue&Volume: 2021-02-22
Abstract: Many natural metalloenzymes assemble from proteins and biosynthesised complexes, generating potent catalysts by changing metal coordination. Here we adopt the same strategy to generate artificial metalloenzymes using ligand exchange to unmask catalytic activity. By systematically testing Ru(II)(η 6 ‐arene)(bipyridine) complexes designed to facilitate the displacement of functionalised bipyridines, we develop a fast and robust procedure for generating new enzymes via ligand exchange in a protein that has not evolved to bind such a complex. The resulting metal cofactors form peptidic coordination bonds but also retain a non‐biological ligand. Tandem mass spectrometry and 19 F NMR spectroscopy were used to characterise the organometallic cofactors and identify the protein‐derived ligands. By introduction of ruthenium cofactors into a 4‐helical bundle, transfer hydrogenation catalysts were generated that displayed a 35‐fold rate increase when compared to the respective small molecule reaction in solution.
DOI: 10.1002/anie.202015834
Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202015834
