厦门大学王斌举团队报道了配位开关驱动非血红素亚砜合成酶选择性C−S键的形成。相关研究成果发表在2022年10月19日出版的国际学术期刊《德国应用化学》。

非血红素铁EgtB是一种亚砜合成酶，催化氧化CS键的形成在合成麦角硫氨酸中起对抗细胞氧化应激的作用。尽管对EgtB的催化机制进行了广泛的实验和计算研究，但选择性CS键形成的根本原因仍然难以捉摸。

该文中，研究人员使用量子力学/分子力学（QM/MM）计算表明亚砜中间体的配位开关参与了非血红素铁EgtB的催化。这种从S到O原子的配位转换是由S/π静电相互作用驱动的，这有效地促进了观察到的立体选择性C-S键的形成，同时绕过了半胱氨酸加氧。本机制与所有可用的实验数据一致，包括区域选择性、立体选择性和KIE结果。该匹配强调了配位开关在非血红素酶催化中的关键作用。

附：英文原文

Title: Coordination Switch Drives Selective C−S Bond Formation by the Non-heme Sulfoxide Synthases

Author: Peng Wu, Yang Gu, Langxing Liao, Yanfei Wu, Jiaoyu Jin, Zhanfeng Wang, Jiahai Zhou, Sason Shaik, Binju Wang

Issue&Volume: 2022-10-19

Abstract: The nonheme iron EgtB is a sulfoxide synthase that catalyzes the oxidative CS bond formation in the synthesis of ergothioneine which plays roles against oxidative stress in cells. Despite the extensive experimental and computational studies of the catalytic mechanisms of EgtB, the root causes for the selective CS bond formation remain elusive. Using quantum mechanics/molecular mechanics (QM/MM) calculations, we show here that coordination switch of the sulfoxide intermediate is involved in the catalysis of the nonheme iron EgtB. Such coordination switch from S to O atom is driven by the S/π electrostatic interactions, which promotes efficiently the observed stereoselective C-S bond formation while bypassing cysteine dioxygenation.  The present mechanism is in agreement with all available experimental data, including regioselectivity, stereoselectivity and KIE results  . This match underscores the critical role of coordination switch in catalysis of non-heme enzymes.

DOI: 10.1002/anie.202214235

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202214235