Current status and future prospects in cannabinoid production through in vitro culture and synthetic biology

Hesami, Mohsen; Pepe, Marco; Baiton, Austin; Jones, Andrew Maxwell Phineas

doi:10.1016/j.biotechadv.2022.108074

Cited by 52 publications

(41 citation statements)

References 208 publications

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“…The current study focuses on “drug-type” cannabis plants that for generations have been cultivated to provide treatments for various medical conditions, including chronic pain [ 5 , 6 ], insomnia [ 7 ], epilepsy [ 8 , 9 ] and dermatological syndromes [ 10 ]. Although the medicinal effect of cannabis is a popular research topic, the development of scientifically based methods for cultivating and breeding advanced cannabis plants for the production of pharmacological substances is still in the early stages [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

Naim-Feil

Elkins

Malmberg

et al. 2023

Plants

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Maintaining specific and reproducible cannabinoid compositions (type and quantity) is essential for the production of cannabis-based remedies that are therapeutically effective. The current study investigates factors that determine the plant’s cannabinoid profile and examines interrelationships between plant features (growth rate, phenology and biomass), inflorescence morphology (size, shape and distribution) and cannabinoid content. An examination of differences in cannabinoid profile within genotypes revealed that across the cultivation facility, cannabinoids’ qualitative traits (ratios between cannabinoid quantities) remain fairly stable, while quantitative traits (the absolute amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV)) can significantly vary. The calculated broad-sense heritability values imply that cannabinoid composition will have a strong response to selection in comparison to the morphological and phenological traits of the plant and its inflorescences. Moreover, it is proposed that selection in favour of a vigorous growth rate, high-stature plants and wide inflorescences is expected to increase overall cannabinoid production. Finally, a range of physiological and phenological features was utilised for generating a successful model for the prediction of cannabinoid production. The holistic approach presented in the current study provides a better understanding of the interaction between the key features of the cannabis plant and facilitates the production of advanced plant-based medicinal substances.

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Section: Introductionmentioning

confidence: 99%

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

Naim-Feil

Elkins

Malmberg

et al. 2023

Plants

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“…Cannabis sativa contains at least 113 cannabinoid compounds; these cannabinoids exhibit a range of unique pharmacological and therapeutic properties. Despite the report of biosynthesis of tetrahydrocannabinolic acid (THCA) (2) and cannabidiolic acid (CBDA) (3) using yeast [ 4 ], the biosynthetic pathways of most of these cannabinoids remain largely unknown, making it difficult for medicinal cannabinoids to be produced in a stable and sustainable manner [ 5 ]. Chemical synthesis of these cannabinoids remains a challenge due to their complex chemical structures.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid Biosynthesis Using Noncanonical Cannabinoid Synthases

Zhu

Lim

et al. 2023

IJMS

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We report enzymes from the berberine bridge enzyme (BBE) superfamily that catalyze the oxidative cyclization of the monoterpene moiety in cannabigerolic acid (CBGA) to form cannabielsoin (CBE). The enzymes are from a variety of organisms and are previously uncharacterized. Out of 232 homologues chosen from the enzyme superfamily, four orthologues were shown to accept CBGA as a substrate and catalyze the biosynthesis of CBE. The four enzymes discovered in this study were recombinantly expressed and purified in Pichia pastoris. These enzymes are the first report of heterologous expression of BBEs that did not originate from the Cannabis plant that catalyze the production of cannabinoids using CBGA as substrate. This study details a new avenue for discovering and producing natural and unnatural cannabinoids.

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“…Hemp ( Cannabis sativa L.) is an annual herbaceous plant of the Cannabaceae family. As one of the oldest domestic crops, hemp has been widely used due to its industrial [ 1 ], ornamental [ 2 ], nutritional [ 3 ], and pharmaceutical [ 4 ] potential. Hempseed oil is a nutrient-rich edible oil with a lipid content of 25–35% and a unique fatty acid (FA) profile characterized by high levels of polyunsaturated fatty acids (PUFAs) and low levels of saturated FAs (SFAs) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification, Classification, and Expression Analyses of the CsDGAT Gene Family in Cannabis sativa L. and Their Response to Cold Treatment

Yan

Chang²,

Gu³

et al. 2023

IJMS

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Hempseed is a nutrient-rich natural resource, and high levels of hempseed oil accumulate within hemp seeds, consisting primarily of different triglycerides. Members of the diacylglycerol acyltransferase (DGAT) enzyme family play critical roles in catalyzing triacylglycerol biosynthesis in plants, often governing the rate-limiting step in this process. As such, this study was designed to characterize the Cannabis sativa DGAT (CsDGAT) gene family in detail. Genomic analyses of the C. sativa revealed 10 candidate DGAT genes that were classified into four families (DGAT1, DGAT2, DGAT3, WS/DGAT) based on the features of different isoforms. Members of the CsDGAT family were found to be associated with large numbers of cis-acting promoter elements, including plant response elements, plant hormone response elements, light response elements, and stress response elements, suggesting roles for these genes in key processes such as development, environmental adaptation, and abiotic stress responses. Profiling of these genes in various tissues and varieties revealed varying spatial patterns of CsDGAT expression dynamics and differences in expression among C. sativa varieties, suggesting that the members of this gene family likely play distinct functional regulatory functions CsDGAT genes were upregulated in response to cold stress, and significant differences in the mode of regulation were observed when comparing roots and leaves, indicating that CsDGAT genes may play positive roles as regulators of cold responses in hemp while also playing distinct roles in shaping the responses of different parts of hemp seedlings to cold exposure. These data provide a robust basis for further functional studies of this gene family, supporting future efforts to screen the significance of CsDGAT candidate genes to validate their functions to improve hempseed oil composition.

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Current status and future prospects in cannabinoid production through in vitro culture and synthetic biology

Cited by 52 publications

References 208 publications

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

Cannabinoid Biosynthesis Using Noncanonical Cannabinoid Synthases

Genome-Wide Identification, Classification, and Expression Analyses of the CsDGAT Gene Family in Cannabis sativa L. and Their Response to Cold Treatment

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