Oxygenase activity in the self-hydroxylation of (S)-2- hydroxypropylphosphonic acid epoxidase involved in fosfomycin biosynthesis

Pinghua Liu, Mark P. Mehn, Feng Yan, Zongbao Zhao, Larry Que, Hung Wen Liu

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31 Scopus citations

Abstract

The last step of the biosynthesis of fosfomycin is the conversion of (S)-2-hydroxypropylphosphonic acid (HPP) to fosfomycin by HPP epoxidase (HppE), which is a mononuclear non-heme iron-dependent enzyme. The apo-HppE from Streptomyces wedmorensis is colorless, but turns green with broad absorption bands at 430 and 680 nm after reconstitution with ferrous ion under aerobic conditions. Resonance Raman studies showed that this green chromophore arises from a bidentate iron(III)-catecholate (DOPA) complex, and the most likely site of modification is at Tyr105 on the basis of site-specific mutagenesis results. It was also found that reconstitution in the presence of ascorbate leads to the formation of additional DOPA that shows 18O-incorporation from 18O2. Thus, HppE can act as an oxygenase via a putative high valent iron-oxo or an iron-hydroperoxo intermediate, just like other members of the family of non-heme iron enzymes. The oxygen activation mechanism for catalytic turnover is proposed to parallel that for self-hydroxylation.

Original languageEnglish (US)
Pages (from-to)10306-10312
Number of pages7
JournalJournal of the American Chemical Society
Volume126
Issue number33
DOIs
StatePublished - Aug 25 2004

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