Identification of key genes involved in secondary metabolite biosynthesis in Digitalis purpurea

Abstract

The medicinal plantDigitalis purpureaproduces cardiac glycosides that are useful in the pharmaceutical industry. These bioactive compounds are in high demand due to ethnobotany’s application to therapeutic procedures. Recent studies have investigated the role of integrative analysis of multi-omics data in understanding cellular metabolic status through systems metabolic engineering approach, as well as its application to genetically engineering metabolic pathways. In spite of numerous omics experiments, most molecular mechanisms involved in metabolic pathways biosynthesis inD.purpurearemain unclear. Using R Package Weighted Gene Co-expression Network Analysis, co-expression analysis was performed on the transcriptome and metabolome data. As a result of our study, we identified transcription factors, transcriptional regulators, protein kinases, transporters, non-coding RNAs, and hub genes that are involved in the production of secondary metabolites. Since jasmonates are involved in the biosynthesis of cardiac glycosides, the candidate genes forScarecrow-Like Protein 14(SCL14),Delta24-sterol reductase(DWF1),HYDRA1(HYD1), and Jasmonate-ZIM domain3 (JAZ3) were validated under methyl jasmonate treatment (MeJA, 100 μM). Despite early induction ofJAZ3, which affected downstream genes, it was dramatically suppressed after 48 hours.SCL14, which targetsDWF1, andHYD1, which induces cholesterol and cardiac glycoside biosynthesis, were both promoted. The correlation between key genes and main metabolites and validation of expression patterns provide a unique insight into the biosynthesis mechanisms of cardiac glycosides inD.purpurea.