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

Author:

Wang Chen1,Chang Wei-chen2,Guo Yisong2,Huang Hui3,Peck Spencer C.4,Pandelia Maria E.2,Lin Geng-min3,Liu Hung-wen3,Krebs Carsten12,Bollinger J. Martin12

Affiliation:

1. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.

2. Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.

3. Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX, USA.

4. Department of Chemistry and the Howard Hughes Medical Institute, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Abstract

Just Add Peroxide The HppE enzyme uses iron to catalyze oxidation of an alcohol to an epoxide ring in the biosynthesis of the antibiotic fosfomycin. Because this process is a two-electron oxidation, it has been unclear how the enzyme reduces its presumed oxidative partner O 2 all the way to water. Where do the two extra electrons come from? Wang et al. (p. 991 , published 10 October; see the Perspective by Raushel ) now show that HppE is actually a peroxidase, and thus reduces H 2 O 2 , for which just two electrons are sufficient. The result expands the structural scope of iron-bearing peroxidase enzymes beyond heme motifs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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