文献类型：期刊文献

英文题名：Biochemical and Structural Characterization of OvoA Th2 : A Mononuclear Nonheme Iron Enzyme from Hydrogenimonas thermophila for Ovothiol Biosynthesis

作者：Wang, Xinye[1];Hu, Sha[2];Wang, Jun[3];Zhang, Tao[2];Ye, Ke[1];Wen, Aiwen[2];Zhu, Guoliang[1];Vegas, Arturo[2];Zhang, Lixin[1];Yan, Wupeng[3];Liu, Xueting[1];Liu, Pinghua[2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Boston Univ, Dept Chem, Boston, MA 02215 USA;[3]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China

年份：2023

卷号：13

期号：23

起止页码：15417

外文期刊名：ACS CATALYSIS

收录：;EI(收录号：20234915186786);WOS:【SCI-EXPANDED(收录号:WOS:001116714800001)】；

基金：This work was supported by the National Key Research and Development Program of China (2019YFA0906201, 2020YFA0907800, 2020YFA090032, 2022YFC2105400), the National Natural Science Foundation of China (32121005, 21977029, 81903529, 32101008, 22307037), the 111 Project (B18022), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, and the Fundamental Research Funds for the Central Universities. This work is supported in part by the National Institutes of Health (GM140040 to P.L.) and the National Science Foundation (CHE-2004109 to P.L.).

语种：英文

外文关键词：nonheme iron enzyme; ovothiol; ergothioneine; X-ray structure; regioselectivity; sulfur-containingnatural products

摘要：Ovothiol A and ergothioneine are thiol-histidine derivatives with sulfur substitutions at the delta-carbon or epsilon-carbon of the l-histidine imidazole ring, respectively. Both ovothiol A and ergothioneine have protective effects on many aging-related diseases, and the sulfur substitution plays a key role in determining their chemical and biological properties, while factors governing sulfur incorporation regioselectivities in ovothiol and ergothioneine biosynthesis in the corresponding enzymes (OvoA, Egt1, or EgtB) are not yet known. In this study, we have successfully obtained the first OvoA crystal structure, which provides critical information to explain their C-S bond formation regioselectivity. Furthermore, OvoA(Th2) exhibits several additional activities: (1) ergothioneine sulfoxide synthase activity akin to Egt1 in ergothioneine biosynthesis; (2) cysteine dioxygenase activity using l-cysteine and l-histidine analogues as substrates; (3) cysteine dioxygenase activity upon mutation of an active site tyrosine residue (Y406). The structural insights and diverse chemistries demonstrated by OvoA(Th2) pave the way for future comprehensive structure-function correlation studies.