Metabolic characterization and transcriptional profiling of polyphenols in Cannabis sativa L. inflorescences with different chemical phenotypes.

Main conclusion: After the most comprehensive analysis of the phenolic composition in Cannabis reported to date, a total of 211 compounds were identified, phenolic profiles were able to discriminate cannabis varieties and a complex regulatory network for phenolics accumulation in Cannabis chemovars was highlighted. Female inflorescences of Cannabis sativa L. are plenty of secondary metabolites, of which flavonoids and phenolic acids have been investigated by far less than phytocannabinoids and terpenoids. Understanding the biochemical composition in phenylpropanoids of Cannabis inflorescences, the molecular basis of flavonoid synthesis and how their content can be modulated by specific transcription factors will shed light on the variability of this trait in the germplasm, allowing the identification of biologically active metabolites that can be of interest to diverse industries. In this work, an untargeted metabolomic approach via UHPLC-HRMS was adopted to investigate the composition and variability of phenylpropanoids in thirteen Cannabis genotypes differentiated for their profile in phytocannabinoids, highlighting that phenolic profiles can discriminate varieties, with characteristic, unique genotype-related patterns. Moreover, the transcription profile of candidate phenolics regulatory MYB and bHLH transcription factors, analyzed by RT-qPCR, appeared strongly genotype-related, and specific patterns were found to be correlated between biochemical and transcriptional levels. Results highlight a complex regulatory network for phenolic accumulation in Cannabis chemovars that will need further insights from the functional side.