Open AccessSingle-Step Replacement of an Unreactive C–H Bond by a C–S Bond Using Polysulfide as the Direct Sulfur Source in the Anaerobic Ergothioneine Biosynthesis
Author(s) -
Ronghai Cheng,
Lian Wu,
Rui Lai,
Chao Peng,
Nathchar Naowarojna,
Weiyao Hu,
Xinhao Li,
Stephen A. Whelan,
Norman Lee,
Juan Lopez,
Changming Zhao,
Youhua Yong,
Jiahui Xue,
Xuefeng Jiang,
Mark W. Grinstaff,
Zixin Deng,
JieSheng Chen,
Qiang Cui,
Jiahai Zhou,
Pinghua Liu
Publication year - 2020
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.0c01809
Subject(s) - ergothioneine , chemistry , polysulfide , sulfur , protonation , catalysis , stereochemistry , organic chemistry , antioxidant , ion , electrode , electrolyte
Ergothioneine, a natural longevity vitamin and antioxidant, is a thiol-histidine derivative. Recently, two types of biosynthetic pathways were reported. In the aerobic ergothioneine biosynthesis, a non-heme iron enzyme incorporates a sulfoxide to an sp 2 C-H bond in trimethyl-histidine (hercynine) through oxidation reactions. In contrast, in the anaerobic ergothioneine biosynthetic pathway in a green sulfur bacterium, Chlorobium limicola , a rhodanese domain containing protein (EanB) directly replaces this unreactive hercynine C-H bond with a C-S bond. Herein, we demonstrate that polysulfide (HSS n SR) is the direct sulfur-source in EanB-catalysis. After identifying EanB's substrates, X-ray crystallography of several intermediate states along with mass spectrometry results provide additional mechanistic details for this reaction. Further, quantum mechanics/molecular mechanics (QM/MM) calculations reveal that protonation of N π of hercynine by Tyr353 with the assistance of Thr414 is a key activation step for the hercynine sp 2 C-H bond in this trans-sulfuration reaction.