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Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase.


ABSTRACT: 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.

SUBMITTER: Wang C 

PROVIDER: S-EPMC4160821 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

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Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase.

Wang Chen C   Chang Wei-chen WC   Guo Yisong Y   Huang Hui H   Peck Spencer C SC   Pandelia Maria E ME   Lin Geng-min GM   Liu Hung-wen HW   Krebs Carsten C   Bollinger J Martin JM  

Science (New York, N.Y.) 20131010 6161


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  ...[more]

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