We assume some biological relationships are fixed and unchangeable.
A rattle snake produces rattle snake venom, a cannabis plant produces cannabinoids, it
seems like an exclusive unidirectional relationship.
Naturally we would not expect these functions to be emulated in say, worms, or by yeasts,
but with the advancement of genetic modification these ‘certainties’ are being challenged
and changed.
Today we’re going to take a look at how scientists hijacked yeast to produce cannabinoids
and what this means for the future of science and medicine!
Currently, cannabinoids such as THC and CBD, which are naturally produced by cannabis are
hot topics.
These compounds are of interest because of their potential therapeutic properties in
a wide variety of contexts including cancer treatments, pain reduction, and mental health
treatment.
However, growing cannabis requires a great deal of time, money and resources.
Even after all that investment, extracting cannabinoids from cannabis is hard and it
is difficult to isolate the particular cannabinoids of interest from others.
This poses difficulties for cannabinoid research.
Luckily, scientists have recently found a way to cut out the middleman, that is the
plant, and get a much simpler model organism to do the work.
In this case they chose Saccharomyces cerevisiae, commonly known as brewer’s yeast.
This species is popular choice because it’s cheap, easy to work with, and has been extensively
studied.
However, this isn’t exactly an easy undertaking.
Needless to say, plants and yeast don’t have too much in common, so to set up a complete
cannabinoid biosynthesis pathway, scientists needed to figure out what steps the Saccharomyces
could and couldn’t do naturally to figure out what genetic modifications were necessary.
Previous work had already managed to modify Saccharomyces allowing it to process GPP and
olivetoic acid into cannabinoids.
However, this only represents the last stages of the biosynthetic pathway.
This time, the goal was to produce cannabinoids from the simplest precursors, sugar and fatty
acids.
Thus, a few extra modifications were needed.
Yeast naturally had some of the capacities needed to process sugars but required a bit
of tweaking to produce adequate levels of GPP.
Additionally, multiple new genes were required to produce olivetoic acid.
CRISPR was used to introduce new genes by teaming up with a guide RNA that recognises
and binds to matching target locations in the Saccharomyces genome.
A cut is made at this site creating room for the desired gene to be inserted and sealed
in.
This super sophisticated system allows for lots of highly specific changes to be made
in a controlled manner, which really sets this experiment apart from previous efforts.
Once integrated into the yeast genome, these new genes sourced from cannabis and different
bacteria could be expressed to produce enzymes that facilitate the reactions that transform
sugars and fats into cannabinoids!
Excitingly, they realised that if they presented Saccharomyces with different types of fatty
acids, different types of cannabinoids would be produced, including novel cannabinoids
that don’t naturally occur or that haven’t yet been observed in cannabis.
These new cannabinoids were modified in ways that effect potency and receptor binding.
Using Saccharomyces allowed for cannabinoids to be more easily isolated, where contamination
is common when working with cannabis.
With increased purity of substances and a whole new set of cannabinoids at our disposal
this process could facilitate much more rigorous research into the specific properties of cannabinoids.
Presently the yield from this process is low but it could well be the precursor to bulk
chemical synthesis of existing and novel cannabinoids.
If this could be achieved, the process would require far less resources and time than that
which goes into horticulture.
This is a beautiful representation of how advanced methods of genetic modification,
such as CRISPR, can be used to recreate complex biosynthetic pathways in simple model organisms.
If this method can be refined further, it could be extended to new contexts.
For instance, the biosynthetic processes behind other medicinal substances such as morphine,
which is derived from poppy seeds, and aspirin, derived frow willow bark, could also be recreated
in simple model organisms.
This could facilitate brand new breakthroughs in science and medicine, pathing the way for
a brighter future!
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