Cannabis sativa L. - Botany and Biotechnology

(Jacob Rumans) #1

the treatment of medical conditions such as epilepsy (cannabidiol; Jones et al. 2012 ;
Devinsky et al. 2014 ), inflammatory bowel disease (cannabigerol; Borrelli et al.
2013 ) and for use as an anti-inflammatory (tetrahydrocannabivarin; Bolognini et al.
2010 ). Several biotechnology companies are now emerging to commercialize
Cannabis products to meet these needs and to explore the potential for less abun-
dant compounds and new cannabinoid-like derivatives as therapeutics.
Librede Inc. (San Diego, CA, USA) is a biotechnology company that specializes
in yeast-based cannabinoid production (http://www.librede.com). The company
was founded in 2009 by University of California scientists who are engineering
yeast with selected portions of cannabinoid biosynthetic pathways. They use a
modular platform for the biosynthesis of natural or synthetic cannabinoid-
derivatives. The technology is based on substituting different enzymes into the
biosynthetic pathway or feeding different intermediates to the yeast to synthesize a
variety of natural cannabinoids. Librede also aims to create pharmaceutically active
cannabinoid-like derivatives by engineering additional enzymatic pathways or
mutating enzymes present in the current pathways. The company expects theirfirst
products to be pure, certified THC and CBD. Subsequently, they aim to produce
personalized formulations containing specified cannabinoid ratios. Hyasynth
Biologicals Inc. (Montreal, QC, Canada) is also engineering yeast to produce
cannabinoids. The company was founded in 2014 and has since successfully pro-
duced cannabigerol (Bell 2016 ). Anandia Laboratories Inc. (Vancouver, BC,
Canada) use genomics and modern plant breeding to improve the therapeutic
properties of Cannabis plants. The company was founded in 2013 and is well
positioned to meet these goals, as the president and CEO, Dr. Jonathan Page, co-led
the groups that mapped thefirst Cannabis genome (van Bakel et al. 2011 ) and owns
patents to several genes involved in the production of cannabinoids (Khamsi 2015 ;
Haag 2016 ). Anandia Labs has partnered with 22nd Century Group Inc., a U.S.
biotechnology company, who intend to engineer tobacco plants as‘biofactories’to
produce cannabinoids (Haag 2016 ).


16.5 Future Opportunities with Cannabis


Gene transfer technologies have played a‘transformative’role in helping to elu-
cidate the main cannabinoid pathway that generates THCA. These technologies
have allowed the over-expression and purification of Cannabis biosynthetic
enzymes in heterologous organisms such asE. coli, tobacco, insect cells and yeast.
Transient and stable expression of Cannabis enzymes in tobacco plants and hairy
root cultures have been made possible byAgrobacterium tumefaciensandA. rhi-
zogenes as gene vectors, respectively. Collectively, these transformation tech-
nologies have enabled genetic and biochemical analyses to identify key enzymes
involved in cannabinoid biosynthesis, to study enzyme function and trafficking.
Results from these studies have provided proof-of-concept that heterologous hosts
can express functional recombinant enzymes in vivo, opening up possibilities for


356 M. Feeney and Z.K. Punja

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