Abstract
During the last decade, the use of medical Cannabis has expanded globally and legislation is getting more liberal in many countries, facilitating the research on cannabinoids. The unique interaction of cannabinoids with the human endocannabinoid system makes these compounds an interesting target to be studied as therapeutic agents for the treatment of several medical conditions. However, currently there are important limitations in the study, production and use of cannabinoids as pharmaceutical drugs. Besides the main constituent tetrahydrocannabinolic acid, the structurally related compound cannabidiol is of high interest as drug candidate. From the more than 100 known cannabinoids reported, most can only be extracted in very low amounts and their pharmacological profile has not been determined. Today, cannabinoids are isolated from the strictly regulated Cannabis plant, and the supply of compounds with sufficient quality is a major problem. Biotechnological production could be an attractive alternative mode of production. Herein, we explore the potential use of synthetic biology as an alternative strategy for synthesis of cannabinoids in heterologous hosts. We summarize the current knowledge surrounding cannabinoids biosynthesis and present a comprehensive description of the key steps of the genuine and artificial pathway, systems biotechnology needs and platform optimization.
Highlights
Cannabinoids enclose a group of more than 100 chemical compounds (Ahmed et al 2008; ElSohly and Slade 2005; Radwan et al 2008) mainly found in the plant Cannabis sativa L., native from Central Asia
In order to rewire the Saccharomyces cerevisiae metabolism for the biosynthesis of cannabinoids, a combined approach comprising the adaptation of native metabolic pathways, the assembly of heterologous metabolic pathways and protein engineering is needed to obtain a cell factory that produces cost-effective cannabinoids
Looking at the biosynthetic pathway of THCA in C. sativa, the pathway can be divided into three parts: (i) geranyl diphosphate (GPP) supply, (ii) synthesis of olivetolic acid (OA) and (iii) the actual cannabinoid formation
Summary
Cannabinoids enclose a group of more than 100 chemical compounds (Ahmed et al 2008; ElSohly and Slade 2005; Radwan et al 2008) mainly found in the plant Cannabis sativa L., native from Central Asia (de Barge 1860; de Candolle 1886). The tendency in literature is to use the designation C. sativa L. to all species or varieties of the genera Cannabis Despite this fact the number of species is not consensual, with some authors proposing a monotypic genus while others argue the existence of four (sativa, indica, ruderalis and afghanica) or even seven It is worth to note that synthetic compounds with no direct structural relation to plant cannabinoids have been designed in the past These synthetic cannabinoids are chemicals developed to interact with the receptors of the ECS and are mostly known as illicit substances.
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