雑誌会（200115）回答_藤田

• REPORT

Evidence that the Fosfomycin-Producing Epoxidase, HppE, Is a Non–Heme-Iron Peroxidase

1. Chen Wang1, 
2. Wei-chen Chang2, 
3. Yisong Guo2, 
4. Hui Huang3, 
5. Spencer C. Peck4, 
6. Maria E. Pandelia2,
7. Geng-min Lin3, 
8. Hung-wen Liu3,*, 
9. Carsten Krebs1,2,*, 
10. J. Martin Bollinger Jr.1,2,*

+Author Affiliations

1. ¹Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
2. ²Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
3. ³Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX, USA.
4. ⁴Department of Chemistry and the Howard Hughes Medical Institute, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

1. ↵*Corresponding author. E-mail: h.w.liu@mail.utexas.edu (H.-w.L.); ckrebs@psu.edu (C.K.); jmb21@psu.edu(J.M.B.)

• ABSTRACT
• EDITOR'S SUMMARY

The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1-phosphonate (S-HPP) to the antibiotic fosfomycin [(1R,2S)-epoxypropylphosphonate] in an unusual 1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been classified as an oxidase, with proposed mechanisms differing primarily in the identity of the O₂-derived iron complex that abstracts hydrogen (H•) from C1 of S-HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate is actually H₂O₂ and that HppE therefore almost certainly uses an iron(IV)-oxo complex as the H• abstractor. Reaction with H₂O₂ is accelerated by bound substrate and produces fosfomycin catalytically with a stoichiometry of unity. The ability of catalase to suppress the HppE activity previously attributed to its direct utilization of O₂ implies that reduction of O₂ and utilization of the resultant H₂O₂ were actually operant.