Institute of Biochemistry, University of Greifswald, Felix-Hausdorff-Str. 4, 17489, Greifswald, Germany.
Dept. of Chemistry, University of Crete, Voutes University Campus, 70013, Heraklion, Greece.
Chembiochem. 2021 Aug 17;22(16):2584-2590. doi: 10.1002/cbic.202100153. Epub 2021 May 10.
Halide methyltransferases (HMTs) enable the enzymatic synthesis of S-adenosyl-l-methionine (SAM) from S-adenosyl-l-homocysteine (SAH) and methyl iodide. Characterisation of a range of naturally occurring HMTs and subsequent protein engineering led to HMT variants capable of synthesising ethyl, propyl, and allyl analogues of SAM. Notably, HMTs do not depend on chemical synthesis of methionine analogues, as required by methionine adenosyltransferases (MATs). However, at the moment MATs have a much broader substrate scope than the HMTs. Herein we provide an overview of the discovery and engineering of promiscuous HMTs and how these strategies will pave the way towards a toolbox of HMT variants for versatile chemo- and regioselective biocatalytic alkylations.
卤代甲基转移酶 (HMTs) 能够催化 S-腺苷-L-同型半胱氨酸 (SAH) 和碘甲烷合成 S-腺苷-L-甲硫氨酸 (SAM)。对一系列天然存在的 HMT 的特征描述和随后的蛋白质工程导致了能够合成 SAM 的乙基、丙基和烯丙基类似物的 HMT 变体。值得注意的是，HMTs 不依赖于蛋氨酸腺苷转移酶 (MATs) 所需的蛋氨酸类似物的化学合成。然而，目前 MATs 的底物范围比 HMTs 广泛得多。本文综述了多功能 HMT 的发现和工程改造，以及这些策略将如何为 HMT 变体的工具包铺平道路，用于多功能化学和区域选择性生物催化烷基化反应。
