Villarino Lara, Chordia Shreyans, Alonso-Cotchico Lur, Reddem Eswar, Zhou Zhi, Thunnissen Andy Mark W H, Maréchal Jean-Didier, Roelfes Gerard
Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
ACS Catal. 2020 Oct 16;10(20):11783-11790. doi: 10.1021/acscatal.0c01619. Epub 2020 Sep 18.
We present an artificial metalloenzyme based on the transcriptional regulator LmrR that exhibits dynamics involving the positioning of its abiological metal cofactor. The position of the cofactor, in turn, was found to be related to the preferred catalytic reactivity, which is either the enantioselective Friedel-Crafts alkylation of indoles with β-substituted enones or the tandem Friedel-Crafts alkylation/enantioselective protonation of indoles with α-substituted enones. The artificial metalloenzyme could be specialized for one of these catalytic reactions introducing a single mutation in the protein. The relation between cofactor dynamics and activity and selectivity in catalysis has not been described for natural enzymes and, to date, appears to be particular for artificial metalloenzymes.
我们展示了一种基于转录调节因子LmrR的人工金属酶，它表现出涉及非生物金属辅因子定位的动力学。反过来，发现辅因子的位置与优选的催化反应性相关，该反应性要么是吲哚与β-取代烯酮的对映选择性傅克烷基化，要么是吲哚与α-取代烯酮的串联傅克烷基化/对映选择性质子化。通过在蛋白质中引入单个突变，人工金属酶可以专门用于这些催化反应之一。天然酶尚未描述辅因子动力学与催化活性和选择性之间的关系，迄今为止，这似乎是人工金属酶所特有的。
