Phytocannabinoids Biosynthesis in Angiosperms, Fungi, and Liverworts and Their Versatile Role

Abstract

Phytocannabinoids are a structurally diverse class of bioactive naturally occurring compounds found in angiosperms, fungi, and liverworts and produced in several plant organs such as the flower and glandular trichrome of Cannabis sativa, the scales in Rhododendron, and oil bodies of liverworts such as Radula species; they show a diverse role in humans and plants. Moreover, phytocannabinoids are prenylated polyketides, i.e., terpenophenolics, which are derived from isoprenoid and fatty acid precursors. Additionally, targeted productions of active phytocannabinoids have beneficial properties via the genes involved and their expression in a heterologous host. Bioactive compounds show a remarkable non-hallucinogenic biological property that is determined by the variable nature of the side chain and prenyl group defined by the enzymes involved in their biosynthesis. Phytocannabinoids possess therapeutic, antibacterial, and antimicrobial properties; thus, they are used in treating several human diseases. This review gives the latest knowledge on their role in the amelioration of abiotic (heat, cold, and radiation) stress in plants. It also aims to provide synthetic and biotechnological approaches based on combinatorial biochemical and protein engineering to synthesize phytocannabinoids with enhanced properties.

Keywords: abiotic stress; cell homeostasis; heterologous host synthetic approach; terpenophenolics.

Figure 1

Structure of phytocannabinoids in Cannabis sativa. Abbreviations: CBC, cannabichromene; CBCA, cannabichromenic acid; CBCV, cannabichromevarine; CBCVA, cannabichromevarinic acid; CBD, cannabidiol; CBDA, cannabidiolic acid; CBDV, cannabidivarine, CBE, cannabielsoin; CBG, cannabigerol; CBL, cannabicyclol; Δ⁸-THC, Δ⁸-tetrahydrocannabinol; Δ⁹-THC, Δ⁹-tetrahydrocannabinol; Δ⁹-THCA, Δ⁹-tetrahydrocannabinolic acid; Δ⁹-THCV, Δ⁹-tetrahydrocannabivarinic acid.

Figure 2

Structure of phytocannabinoids in Helichrysum and Glycyrrhiza plants.

Figure 3

Structure of phytocannabinoids in Rhododendron plants.

Figure 4

Structure of phytocannabinoids in (a) liverworts and (b) fungi.

Figure 5

Phytocannabinoids biosynthesis in Cannabis sativa. Abbreviations: CBCA, cannabichromenic acid; CBCAS, cannabichromenic acid synthase; CBDA, cannabidiolic acid; CBDAS, cannabidiolic acid synthase; Δ⁹-THCA, Δ⁹-tetrahydrocannabinolic acid; Δ⁹-THCAS, Δ⁹-tetrahydrocannabinolic acid synthase.

Figure 6

Phytocannabinoids biosynthesis in Rhododendron. Abbreviations: DCAS, daurichromenic acid synthase; MEP, methylerythritol-4-phosphate; PT, prenyltransferase.

Figure 7

Phytocannabinoids biosynthesis in liverworts. Abbreviations: C4H, cinnamate 4-hydroxylase; 4CL, 4-coumarate:CoA ligase; PAL, phenylalanine ammonia-lyase; TAL, tyrosine ammonia-lyase.

Figure 8

Selective role of active phytocannabinoids in humans, mammals, plants, biotechnology, and industries. Abbreviations: CBC, cannabichromene; CBCA, cannabichromenic acid; CBD, cannabidiol; CBDA, cannabidiolic acid; CBG, cannabigerol; CBGA, cannabigerolic acid; CBN, cannabinol; CBR, cannabinoid receptor; DCA, daurichromenic acid; PA, perrottetinenic acid; Δ⁹-THC, Δ⁹-tetrahydrocannabinol.