A phenotype-directed chemical screen identifies ponalrestat as an inhibitor of the plant flavin monooxygenase YUCCA in auxin biosynthesis

Ying Zhu,Hong-Jiang Li,Qi Su,Jing Wen,Yuefan Wang,Wen Song,Yinpeng Xie,Wenrong He,Zhen Yang,Kai Jiang,Hongwei Guo

doi:10.1074/jbc.ra119.010480

Abstract

Plant development is regulated by both synergistic and antagonistic interactions of different phytohormones, including a complex crosstalk between ethylene and auxin. For instance, auxin and ethylene synergistically control primary root elongation and root hair formation. However, a lack of chemical agents that specifically modulate ethylene or auxin production has precluded precise delineation of the contribution of each hormone to root development. Here, we performed a chemical genetic screen based on the recovery of root growth in ethylene-related Arabidopsis mutants with constitutive "short root" phenotypes (eto1-2 and ctr1-1). We found that ponalrestat exposure recovers root elongation in these mutants in an ethylene signal-independent manner. Genetic and pharmacological investigations revealed that ponalrestat inhibits the enzymatic activity of the flavin-containing monooxygenase YUCCA, which catalyzes the rate-limiting step of the indole-3-pyruvic acid branch of the auxin biosynthesis pathway. In summary, our findings have identified a YUCCA inhibitor that may be useful as a chemical tool to dissect the distinct steps in auxin biosynthesis and in the regulation of root development.

Highlights

Plant development is regulated by both synergistic and antagonistic interactions of different phytohormones, including a complex crosstalk between ethylene and auxin
We found that ponalrestat treatment suppressed root hair formation (Fig. 3A) and interrupted root gravitropic growth (Fig. 3, B and C), with similar changes observed in eto1–2, ctr1–1, and EIN3 overexpression line (EIN3ox) mutants (Fig. S2)
We performed a phenotype-directed screen using ethylene signaling-activated mutants and found that ponalrestat, an inhibitor of human aldose reductase, could rescue the short root phenotype induced by the ethylene signal (Fig. 1 and Fig. S1)

Summary

Introduction

Plant development is regulated by both synergistic and antagonistic interactions of different phytohormones, including a complex crosstalk between ethylene and auxin. A lack of chemical agents that modulate ethylene or auxin production has precluded precise delineation of the contribution of each hormone to root development. Our findings have identified a YUCCA inhibitor that may be useful as a chemical tool to dissect the distinct steps in auxin biosynthesis and in the regulation of root development. 3 Present address: School of Pharmacy, North Sichuan Medicine College, Nanchong 637100 China. 5 Present address: State Key Laboratory of Chemical Oncogenomics and Key. Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 China.

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Conclusion