4-hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase: 2-oxo acid-dependent oxygenases of importance to agriculture and medicine

Dhara D. Shah, Graham R. Moran

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Despite a separate evolutionary lineage, 4-hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate synthase (HMS) are appropriately grouped with the 2-oxo acid-dependent oxygenase (2OADO) family of enzymes. HPPD and HMS accomplish highly similar overall chemistry to that observed in the majority of 2OADOs but require only two substrates rather than three. 2OADOs typically use the 2-oxo acid of 2-oxoglutarate (2OG) as a source of electrons to reduce and activate dioxygen in order to oxidize a third specific substrate. HPPD and HMS use instead the pyruvate substituent of 4-hydroxyphenylpyruvate to activate dioxygen and then proceed to also hydroxylate this substrate, each yielding a distinctly different aromatic product. HPPD catalyses the second and committed step of tyrosine catabolism, a pathway common to nearly all aerobes. Plants require the HPPD reaction to biosynthesize plastoquinones and therefore HPPD inhibitors can have potent herbicidal activity. The ubiquity of the HPPD reaction, however, has meant that HPPD-specific molecules developed as herbicides have other uses in different forms of life. In humans herbicidal HPPD inhibitors can be used therapeutically to alleviate specific inborn defects and also to retard the progress of certain bacterial and fungal infections. This review is intended as a concise overview of the contextual and catalytic chemistries of HPPD and HMS.

Original languageEnglish (US)
Title of host publication2-Oxoglutarate-Dependent Oxygenases
EditorsRobert P. Hausinger, Christopher J. Schofield
PublisherRoyal Society of Chemistry
Pages438-457
Number of pages20
Edition3
DOIs
StatePublished - 2015
Externally publishedYes

Publication series

NameRSC Metallobiology
Number3
Volume2015-January
ISSN (Print)2045-547X

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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