Overexpression of HMG-CoA synthase promotes Arabidopsis root growth and adversely affects glucosinolate biosynthesis

J Exp Bot. 2020 Jan 1;71(1):272-289. doi: 10.1093/jxb/erz420.


3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the second step of the mevalonate (MVA) pathway. An HMGS inhibitor (F-244) has been reported to retard growth in wheat, tobacco, and Brassica juncea, but the mechanism remains unknown. Although the effects of HMGS on downstream isoprenoid metabolites have been extensively reported, not much is known on how it might affect non-isoprenoid metabolic pathways. Here, the mechanism of F-244-mediated inhibition of primary root growth in Arabidopsis and the relationship between HMGS and non-isoprenoid metabolic pathways were investigated by untargeted SWATH-MS quantitative proteomics, quantitative real-time PCR, and target metabolite analysis. Our results revealed that the inhibition of primary root growth caused by F-244 was a consequence of reduced stigmasterol, auxin, and cytokinin levels. Interestingly, proteomic analyses identified a relationship between HMGS and glucosinolate biosynthesis. Inhibition of HMGS activated glucosinolate biosynthesis, resulting from the induction of glucosinolate biosynthesis-related genes, suppression of sterol biosynthesis-related genes, and reduction in sterol levels. In contrast, HMGS overexpression inhibited glucosinolate biosynthesis, due to down-regulation of glucosinolate biosynthesis-related genes, up-regulation of sterol biosynthesis-related genes, and increase in sterol content. Thus, HMGS might represent a target for the manipulation of glucosinolate biosynthesis, given the regulatory relationship between HMGS in the MVA pathway and glucosinolate biosynthesis.

Keywords: Arabidopsis; F-244; HMGS; glucosinolate; isoprenoid; mevalonate; primary root; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / enzymology
  • Arabidopsis / genetics*
  • Arabidopsis / growth & development
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Plant*
  • Glucosinolates / biosynthesis*
  • Hydroxymethylglutaryl-CoA Synthase / genetics*
  • Hydroxymethylglutaryl-CoA Synthase / metabolism
  • Plant Roots / genetics
  • Plant Roots / growth & development*
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / growth & development


  • Arabidopsis Proteins
  • Glucosinolates
  • Hydroxymethylglutaryl-CoA Synthase