Comparative transcriptomics reveals candidate transcription factors involved in costunolide biosynthesis in medicinal...

Costunolides, an important sesquiterpene lactone (STL) isolated from Saussurea lappa, are the major pharmaceutical ingredient of various drug formulations. Identification of the genes and transcriptional regulation of costunolide biosynthesis pathway in S. lappa will propose alternatives for engineering enhanced metabolite biosynthesis in plant. Here, we aimed to unravel the transcription factors (TFs) regulating the costunolide biosynthesis. Comparative transcriptome analysis of root and leaf tissues and transcripts were annotated using various in silico tools. Putative transcription factors were identified using PlantTFDB and TF- gene co-expression network was generated followed by clustering using module based analysis to observe their coordinated behaviour. The module 1 was found to be significant based on its enrichment with major pathway genes. Further, promoter cloning determined the cis acting elements in costunolide synthase (SlCOS1) gene which catalyses the final key step of costunolide biosynthesis. Bioinformatics tools were employed to predict the cis regulatory elements, leading to the identification of MYB family of TFs as an interacting partner of SlCOS1 gene. The present study is the pioneer attempt for TF prediction and elucidation of their regulatory role in costunolide synthesis. This will help in future metabolic engineering of the pharmaceutically important STLs and their yield improvement.