Skip to main content
Canna~Fangled Abstracts

Biosynthesis of Nature-Inspired Unnatural Cannabinoids

By May 14, 2021June 6th, 2021No Comments
Review
. 2021 May 14;26(10):2914.

doi: 10.3390/molecules26102914.

Kevin J H Lim 1 2 3 4, Yan Ping Lim 1 2 3, Yossa D Hartono 1 2 3 4, Maybelle K Go 1 2 3, Hao Fan 1 2 4, Wen Shan Yew 1 2 3
Affiliations 

Free PMC article

Abstract

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.

 

Keywords: Cannabis sativa, cannabinoid receptors, cannabinoids biosynthesis, drug design, metabolic engineering, natural products, synthetic enzymology

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

References

    1. Patridge E., Gareiss P., Kinch M.S., Hoyer D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discov. Today. 2016;21:204–207. doi: 10.1016/j.drudis.2015.01.009. – DOI – PubMed
    1. Appendino G., Gibbons S., Giana A., Pagani A., Grassi G., Stavri M., Smith E., Rahman M.M. Antibacterial cannabinoids from Cannabis sativa: A structure-activity study. J. Nat. Prod. 2008;71:1427–1430. doi: 10.1021/np8002673. – DOI – PubMed
    1. Pryce G., Riddall D.R., Selwood D.L., Giovannoni G., Baker D. Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids. J. Neuroimmune Pharmacol. 2015;10:281–292. doi: 10.1007/s11481-014-9575-8. – DOI – PubMed
    1. Velasco G., Sanchez C., Guzman M. Towards the use of cannabinoids as antitumour agents. Nat. Rev. Cancer. 2012;12:436–444. doi: 10.1038/nrc3247. – DOI – PubMed
    1. Gulck T., Moller B.L. Phytocannabinoids: Origins and Biosynthesis. Trends Plant Sci. 2020 doi: 10.1016/j.tplants.2020.05.005. – DOI – PubMed

Publication types

LinkOut – more resources

Leave a Reply