Ngā Hua Tuhituhi
Papers, presentations and project pānui from Te Puna Mātauranga o Wairuakohu
Dr Richard Espley from Plant & Research discussed the project on Radio NZ – 17 January 2025
Unique bibenzyl cannabinoids in the liverwort Radula marginata: parallels with Cannabis chemistry
New Phytologist (December 2024)
Christelle Andre, Catherine Sansom, Blue Plunkett, Cyril Hamiaux, Lenhy Massey, Andrew Chan; Manu Caddie, Richard Espley, Nigel Perry
Demand for novel cannabinoids has stimulated exploration into new sources and sustainable production technologies. Radula marginata, an endemic New Zealand liverwort, has unique bibenzyl cannabinoids: perrottetinene (cis-PET), analogous to tetrahydrocannabinol (trans-THC), the primary psychoactive in Cannabis sativa. PET’s cis stereochemistry, opposite to that of THC, and its bibenzyl backbone, have potential therapeutic benefits, mitigating adverse side effects.
This study analysed R. marginata cannabinoid chemistry of 75 collections from several sites and seasons, working with Māori kaitiaki. The metabolic plasticity of the cannabinoids and plant growth was assessed after transplantation into controlled growth conditions, and in vitro culture.
These results expand cannabinoid knowledge, identifying two “new” cannabinoid bibenzyls. The discovery adds a new dimension to liverwort cannabinoids and suggests convergent evolution of biosyntheses in two distant plant lineages.
Demystifying the liverwort Radula marginata, a critical review on its taxonomy, genetics, cannabinoid phytochemistry and pharmacology
Springer Nature B.V. (2019)
Tajammul Hussain, Richard V. Espley, Jürg Gertsch, Tracey Whare, Felix Stehle, Oliver Kayser
Radula marginata is a subtropical liverwort, endemic to the Northern island of New Zealand in the Pacific region. Despite its significant potential as an alternative source of a THC-like phytocannabinoid, the biosynthesis of this compound remains elusive. Following the discovery of a bibenzyl cis-tetrahydrocannabinol (perrottetinene) in R. marginata, research has focused on genetic fingerprinting
and transcriptomic analysis for the genes involved in its biosynthesis. More recently, its pharmacological activity with the endocannabinoid receptors (CB1 and CB2) has been demonstrated, paving the way to more extensive research on this liverwort. Here, we provide an in-depth review of the current research.
Firstly, we describe the taxonomy and phytogeography of R. marginata, followed by the symbiosis and evolutionary aspects of bryophytes in general, with a specific focus on liverworts. We then review the physiology and anatomy from scanning electron microscopy data. The presence of the oil bodies and their functional insights for the storage of secondary metabolites, such as perrottetinene, are illustrated. We review the available genetic and transcriptomic resources for R.marginata.
We discuss pharmacological aspects of the natural bi-benzyl cis-perrottetinene as compared to THC. The reported partial agonistic activity of this compound at CB1 and CB2 receptors, and the need for further study for the treatment of inflammatory conditions, is considered. Moreover, given that THC has beneficial effects topically, we discuss the potential use of R. marginata for dermatological conditions.
Finally, we elaborate on the ethnobotanical aspects and the legal and ethical position of plant collection in New Zealand. Overall, this review gives the first detailed overview of R. marginata. We include the morphology, taxonomy, anatomy, physiology, evolution as well as the genetic basis linking it with electron microscopic studies and its biological effects.
Identification of Putative Precursor Genes for the Biosynthesis of Cannabinoid-Like Compound in Radula marginata
Frontiers in Plant Science (2018)
Tajammul Hussain, Blue Plunkett, Mahwish Ejaz, Richard V. Espley, Oliver Kayser
The liverwort Radula marginata belongs to the bryophyte division of land plants and is a prospective alternate source of cannabinoid-like compounds. However, mechanistic insights into the molecular pathways directing the synthesis of these cannabinoid-like compounds have been hindered due to the lack of genetic information. This prompted us to do deep sequencing, de novo assembly and annotation of R. marginata transcriptome, which resulted in the identification and validation of the genes for cannabinoid biosynthetic pathway. In total, we have identified 11,421 putative genes encoding 1,554 enzymes from 145 biosynthetic pathways. Interestingly, we have identified all the upstream genes of the central precursor of cannabinoid biosynthesis, cannabigerolic acid (CBGA), including its two first intermediates, stilbene acid (SA) and geranyl diphosphate (GPP). Expression of all these genes was validated using quantitative real-time PCR. We have characterized the protein structure of stilbene synthase (STS), which is considered as a homolog of olivetolic acid in R. marginata. Moreover, the metabolomics approach enabled us to identify CBGA-analogous compounds using electrospray ionization mass spectrometry (ESI-MS/MS) and gas chromatography mass spectrometry (GC-MS). Transcriptomic analysis revealed 1085 transcription factors (TF) from 39 families. Comparative analysis showed that six TF families have been uniquely predicted in R. marginata. In addition, the bioinformatics analysis predicted a large number of simple sequence repeats (SSRs) and non-coding RNAs (ncRNAs). Our results collectively provide mechanistic insights into the putative precursor genes for the biosynthesis of cannabinoid-like compounds and a novel transcriptomic resource for R. marginata. The large-scale transcriptomic resource generated in this study would further serve as a reference transcriptome to explore the Radulaceae family.