In vivo fluorescent screening for HPPD-targeted herbicide discovery

Pest Manag Sci. 2022 Nov;78(11):4947-4955. doi: 10.1002/ps.7117. Epub 2022 Aug 25.

Abstract

Background: 4-Hydroxyphenylpyruvate dioxygenase (HPPD), playing a critical role in vitamin E and plastoquinone biosynthesis in plants, has been recognized as one of the most important targets for herbicide discovery for over 30 years. Structure-based rational design of HPPD inhibitors has received more and more research interest. However, a critical challenge in the discovery of new HPPD inhibitors is the common inconsistency between molecular-level HPPD-based bioevaluation and the weed control efficiency in fields, due to the unpredictable biological processes of absorption, distribution, metabolism, and excretion.

Results: In this study, we developed a fluorescent-sensing platform of efficient in vivo screening for HPPD-targeted herbicide discovery. The refined sensor has good capability of in situ real-time fluorescence imaging of HPPD in living cells and zebrafish. More importantly, it enabled the direct visible monitoring of HPPD inhibition in plants in a real-time manner.

Conclusion: We developed a highly efficient in vivo fluorescent screening method for HPPD-targeted herbicide discovery. This discovery not only offers a promising tool to advance HPPD-targeted herbicide discovery, but it also demonstrates a general path to develop the highly efficient, target-based, in vivo screening for pesticide discovery. © 2022 Society of Chemical Industry.

Keywords: 4-hydroxyphenylpyruvate dioxygenase; fluorescent sensors; herbicide; imaging.

MeSH terms

  • 4-Hydroxyphenylpyruvate Dioxygenase*
  • Animals
  • Dioxygenases*
  • Enzyme Inhibitors / pharmacology
  • Herbicides* / pharmacology
  • Plants / metabolism
  • Plastoquinone
  • Vitamin E
  • Zebrafish / metabolism

Substances

  • Enzyme Inhibitors
  • Herbicides
  • Vitamin E
  • Dioxygenases
  • 4-Hydroxyphenylpyruvate Dioxygenase
  • Plastoquinone