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Reaction of HppE with substrate analogues: evidence for carbon-phosphorus bond cleavage by a carbocation rearrangement.

ABSTRACT: (S)-2-hydroxypropylphosphonic acid ((S)-2-HPP) epoxidase (HppE) is an unusual mononuclear non-heme iron enzyme that catalyzes the oxidative epoxidation of (S)-2-HPP in the biosynthesis of the antibiotic fosfomycin. Recently, HppE has been shown to accept (R)-1-hydroxypropylphosphonic acid as a substrate and convert it to an aldehyde product in a reaction involving a biologically unprecedented 1,2-phosphono migration. In this study, a series of substrate analogues were designed, synthesized, and used as mechanistic probes to study this novel enzymatic transformation. The resulting data, together with insights obtained from density functional theory calculations, are consistent with a mechanism of HppE-catalyzed phosphono group migration that involves the formation of a carbocation intermediate. As such, this reaction represents a new paradigm for biological C-P bond cleavage.

SUBMITTER: Chang WC

PROVIDER: S-EPMC3796158 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Reaction of HppE with substrate analogues: evidence for carbon-phosphorus bond cleavage by a carbocation rearrangement.

Chang Wei-chen WC Mansoorabadi Steven O SO Liu Hung-wen HW

Journal of the American Chemical Society 20130523 22

(S)-2-hydroxypropylphosphonic acid ((S)-2-HPP) epoxidase (HppE) is an unusual mononuclear non-heme iron enzyme that catalyzes the oxidative epoxidation of (S)-2-HPP in the biosynthesis of the antibiotic fosfomycin. Recently, HppE has been shown to accept (R)-1-hydroxypropylphosphonic acid as a substrate and convert it to an aldehyde product in a reaction involving a biologically unprecedented 1,2-phosphono migration. In this study, a series of substrate analogues were designed, synthesized, and ...[more]

PMID: 23672451

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