Integrating metabolomics and transcriptomics to unveil the spatiotemporal distribution of macrocyclic diterpenoids and candidate genes involved in ingenol biosynthesis in the medicinal plant Euphorbia lathyris L.

Abstract

Macrocyclic diterpenoids, such as ingenol, are the main bioactive ingredients in Euphorbia lathyris L. Ingenol is the precursor for industrial production of ingenol-3-angelate, which was approved for the treatment of actinic keratosis in 2012. However, the distribution and biosynthesis of macrocyclic diterpenoids, especially ingenol, during the growth cycle of E. lathyris L. are largely unknown. To investigate the dynamics of the distribution of macrocyclic diterpenoids in different tissues across the entire life cycle of E. lathyris L. and candidate genes involved in their biosynthesis, combined metabolome-transcriptome analysis was performed. A total of 144 samples collected from different tissues covering the whole life cycle of E. lathyris L. were detected by high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). Next, 67 macrocyclic diterpenoids were profiled via MS/MS characteristic ions, and their dynamic distributions were analyzed. The results indicated that macrocyclic diterpenoids mainly accumulated in the roots and seeds of E. lathyris L. To gain insight into ingenol biosynthesis, transcriptome sequencing of different tissues from mature E. lathyris L. was carried out, and a total of 50,177 − 69,999 unigenes were annotated. Subsequently, weighted gene coexpression network analysis (WGCNA) was performed, candidate genes with high potential of involvement in ingenol biosynthesis were obtained. This study provides a basis for further research and utilization of macrocyclic diterpenoids in E. lathyris L. and benefits the green production of ingenol.