An S=1 Iron(IV) Intermediate Revealed in a Non-Heme Iron Enzyme-Catalyzed Oxidative C-S Bond Formation.

Autor: Paris JC; Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213, USA., Hu S; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Wen A; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Weitz AC; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Cheng R; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Gee LB; LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Rd., Menlo Park, CA 94025, USA., Tang Y; Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213, USA., Kim H; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Vegas A; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Chang WC; Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA., Elliott SJ; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Liu P; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA., Guo Y; Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Oct 23; Vol. 62 (43), pp. e202309362. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1002/anie.202309362
Abstrakt: Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol-histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O 2 -dependent C-S bond formation catalyzed by non-heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S=1 iron(IV) intermediate supported by a four-histidine ligand environment (three from the protein residues and one from the substrate) in enabling C-S bond formation in OvoA from Methyloversatilis thermotoleran, which represents the first experimentally observed intermediate spin iron(IV) species in non-heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C-S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure-function relationship of high-valent iron intermediates supported by a histidine rich ligand environment.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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