Mevinolin (MEV) modulates terpenoid biosynthesis in 'Shine Muscat' grapes by regulating HMGR enzyme

Mevinolin (MEV) is an inhibitor of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR), which is a crucial enzyme in terpenoid biosynthesis. Since there is limited understanding of the impact of MEV on fruit quality, this study characterized the influence of MEV on metabolism in 'Shine Muscat' grapes at the softening stage through an integrated multi-omics analysis. After 7 days of MEV treatment, HMGR and FPPS enzyme activities decreased, accompanied by down-regulation of genes HMGR1, HMGR2, and FPS, while HMGR3 was up-regulated. In the MEP pathway, the activities of key enzymes DXS, TPS, and GGPPS increased, along with upregulation of genes DXR and GGPPS. MEV treatment significantly affected resveratrol and phenolics accumulation, with resveratrol decreasing 3 days post-treatment but elevated after 7 days; however, phenolics were consistently downregulated. Intriguingly, total flavonoids were not significantly affected. Transcriptome analysis showed that MEV upregulated the majority of differentially expressed genes (DEGs), directly affecting ubiquinone and other terpenoid quinone biosynthesis and sesquiterpenoid/triterpenoid biosynthesis pathways. Additionally, MEV treatment also modulated the metabolism of phytohormones, particularly SA, IAA, ETH, and GA. Analysis of volatile metabolites showed that MEV treatment reduced the contents of verbenol and 4-Hexen-1-ol 5-methyl-2-(1-methylethenyl)-,(R)- (Lavandulol), which were related to the cherry and fresh flavors of grapes. Verbenol was positively correlated with Gibberellin 2-beta-dioxygenase8 (GA2ox8), while Lavandulol was negatively correlated with Caffeoyl-CoA O-methyltransferase and beta amylin synthase 1 (β-AS). Specific analysis of terpenoid metabolites revealed that MEV treatment significantly altered 14 terpenoid metabolites, including diterpenoids, sesquiterpenoids, and monoterpenoids, while showing minimal or no effect on triterpenes. Integrated transcriptome analysis demonstrated that isopimaric acid showed strong correlation with the genes alcohol dehydrogenase 1 (ADH1) and geraniol 8-hydroxylase (G8H), with expression patterns significantly altered by MEV treatment. Notably, G8H was negatively correlated with most genes and metabolites. Overall, these findings demonstrate that MEV substantially influences terpenoid biosynthesis and metabolism in "Shine Muscat" grape fruits.