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Amallia Darwis, Dina

Chua, Elvis

Dwi Hartono, Yossa

Fan, Hao

Jia, Xinying

Lim, Yan Ping

Suan Jasmine Chua, Puay

Wong, Garrett

Xue, Bo

Yew, Wen Shan

Zhu, Tingting

English

Engineering Conferences International

CANNABINOID BIOSYNTHESIS USING NON-CANONICAL ENZYMES  Yan Ping Lim, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) bchlimy@nus.edu.sg Tingting Zhu, NUS SynCTI Yossa Dwi Hartono, NUS SynCTI Bo Xue, NUS SynCTI Puay Suan Jasmine Chua, NUS SynCTI Xinying Jia, NUS SynCTI Elvis Chua, NUS SynCTI Garrett Wong, NUS SynCTI Dina Amallia Darwis, NUS SynCTI Hao Fan, Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR) Wen Shan Yew, NUS SynCTI   Key Words: Cannabinoids, Prenyltransferases, Cannabielsoin, Synthetic Biology.  Cannabinoids are secondary metabolites naturally found in the trichomes and flower buds of Cannabis plants. Recent legalisation of cannabinoid usage in several countries have brought up the market demand and interest in cannabinoid related research. Yet, there is a lack of sustainable production methods. Major cannabinoids such as (-)-∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) have been studied over the years for pharmacological properties such as antidepressant, analgesic, and anti-inflammatory properties. Meanwhile, more than 90% of the phytocannabinoids spectrum comprises minor cannabinoids that are often overlooked. The low abundance of natural minor cannabinoids greatly hinders their accessibilities to further medicinal evaluation.   To circumvent this issue, we propose an approach by synthetic biology to establish alternative cannabinoid production methods in microbial hosts. The versatility of genetic engineering technology to tailor-make microbial cell factories can potentially empower the production of desired cannabinoids at an economically viable level. We focus on enzymatic conversions that involve the formation of the first committed metabolite in the cannabinoid biosynthetic pathway, cannabigerolic acid (CBGA), and its subsequent conversion to downstream cannabinoid products. In particular, we have identified three novel promiscuous prenyltransferases which have high yields of CBGA, as well as the ability to produce non-canonical cannabinoid precursors via alternate prenylation activities. In addition, we report the identification of three non-canonical cannabinoid synthases (CBS) from the berberine bridge enzyme family (BBE) that accept CBGA as a substrate and produce cannabielsoin (CBE). In conclusion, our research details a new avenue for discovering and producing both natural and unnatural cannabinoids.   Figure 1 – Proposed cannabinoid biosynthetic pathway to produce both natural and unnatural cannabinoids. 

Cannabinoid biosynthesis using non-canonical enzymes

https://dc.engconfintl.org/cgi/viewcontent.cgi?filename=0&article=1103&context=enzyme_xxvii&type=additional

Cannabinoid biosynthesis using non-canonical enzymes

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Engineering Conferences International