The effect of 3-hydroxy-3-methylglutaryl-CoA synthase extends beyond the isoprenoid pathway

Abstract

The mevalonate (MVA) pathway generates isoprenoids including phytosterols. Dietary phytosterols are important because they can lower blood cholesterol levels. In the MVA pathway, 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the condensation of acetoacetyl-CoA and acetyl-CoA to form HMG-CoA. Previous studies have shown that the recombinant Brassica juncea HMGS1 (BjHMGS1) mutant S359A displayed 10-fold higher enzyme activity than wild-type (wt) BjHMGS1 while transgenic tobacco S359A-overexpressors (OE-S359A) accumulated sterol content, and possessed higher growth rate and seed yield than OE-wtBjHMGS1. Herein, omics methods were employed to understand the differences brought about by HMGS overexpression. Comparative transcriptomics analysis verified that the improved effect of OE-S359A resulted from an increase in downstream isoprenoid biosynthesis-, primary metabolismand plant hormone-related gene expression. Proteomics and metabolomics data will be discussed to demonstrate that HMGS links the MVA pathway to the central metabolic pathways.