4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Chemical Biology to Agrochemicals

J Agric Food Chem. 2017 Oct 4;65(39):8523-8537. doi: 10.1021/acs.jafc.7b03851. Epub 2017 Sep 25.

Abstract

The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an enzyme engaged in photosynthetic activity and catalyzes the transformation of 4-hydroxyphenylpyruvic acid (HPPA) into homogentisic acid (HGA). HPPD inhibitors constitute a promising area of discovery and development of innovative herbicides with some advantages, including excellent crop selectivity, low application rates, and broad-spectrum weed control. HPPD inhibitors have been investigated for agrochemical interests, and some of them have already been commercialized as herbicides. In this review, we mainly focus on the chemical biology of HPPD, discovery of new potential inhibitors, and strategies for engineering transgenic crops resistant to current HPPD-inhibiting herbicides. The conclusion raises some relevant gaps for future research directions.

Keywords: 4-hydroxyphenylpyruvate dioxygenase; agrochemical; chemical biology; herbicide; inhibitor.

Publication types

  • Review

MeSH terms

  • 4-Hydroxyphenylpyruvate Dioxygenase / antagonists & inhibitors*
  • 4-Hydroxyphenylpyruvate Dioxygenase / chemistry
  • 4-Hydroxyphenylpyruvate Dioxygenase / metabolism*
  • Agrochemicals* / chemistry
  • Agrochemicals* / pharmacology
  • Arabidopsis / enzymology
  • Catalysis
  • Drug Resistance
  • Enzyme Inhibitors* / pharmacology
  • Herbicides* / chemistry
  • Herbicides* / pharmacology
  • Homogentisic Acid / metabolism
  • Molecular Structure
  • Phenylpyruvic Acids / metabolism
  • Plants, Genetically Modified / drug effects
  • Recombinant Proteins
  • Structure-Activity Relationship
  • Weed Control

Substances

  • Agrochemicals
  • Enzyme Inhibitors
  • Herbicides
  • Phenylpyruvic Acids
  • Recombinant Proteins
  • 4-hydroxyphenylpyruvic acid
  • 4-Hydroxyphenylpyruvate Dioxygenase
  • Homogentisic Acid