Work

Reaction of HppE with Substrate Analogues: Evidence for Carbon–Phosphorus Bond Cleavage by a Carbocation Rearrangement

Year: 2013

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja403441x

Authors: Wei-chen Chang, Steven O. Mansoorabadi, Hung-wen Liu

Institution: The University of Texas at Austin

Language: English

Topic: Chemical Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Award: Investigation of Unusual Cyclization Reactions in Biocatalysis