Why stress test this medium for cannabinoid biosynthesis with a disease?

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When you buy a product, like a car tire or a light switch, it has likely gone through a stress test. That is, a test simulates years of use to ensure a design can withstand any conditions it might face. Similarly, a cannabis crop can consist of disease-resistant genetics that can yield good profiles. For yeast engineered to produce THC or methyl-CBD, for example, can a disease that affects cannabinoid biosynthesis work as a stress test?

Neurodegenerative diseases and cannabinoids

A mutant human gene causes Huntington’s Disease. Moreover, the early stages of the neurodegenerative disease mostly include severe CB1 receptor depletion. (1) For this reason, Huntington’s Disease helps us understand the endocannabinoid system. Yet, the origins of CB receptors have no relation to the biosynthesis of cannabinoids. And so, infecting a yeast with Huntington’s might not be a good stress test for THC production.

Parkinson’s Disease also affects the ECS, though. (2) Genes commonly studied in artificial yeast models produce proteins responsible for PD. One study noted effects on certain cellular functions. (3) And one of those functions directly influences a novel cannabinoid biosynthesis stream patented by Hyasynth Biologicals. (4, 5)

Infectious proteins and cellular lipids

Transport networks allow for the movement of lipids — including endocannabinoids — within cells. Proteins that cause Parkinson’s Disease, however, further disrupt cellular switches as well as critical lipid transit systems. (3, 5, 6) While the process cannot be recommended for production due to potential public health risks. Infecting yeast with Parkinson’s Disease by engineering it to produce alpha-synuclein, therefore, might function as a stress test for cannabinoid biosynthesis.

Albeit, scientific experiments frequently work with yeast models of Parkison’s Disease. (3) The concern with the concept is still, of course, containment. On a scale for research and development, this does not breach normal procedures. For production, though, the cannabinoid industry appears to be drenched in regulations. But are novel processes potentially employed in cannabinoid biosynthesis truly considered by the same lawmakers who authorize the use of chloropicrin?

Let us know in the comments if you think tests covering cannabinoid biosynthesis in a medium of yeast or bacteria should be better established.

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  • In yeast, alpha-synuclein (the protein that causes Parkison’s and Lewy Body Dementia) aggregates Rab GTPase proteins, including Ypt6.
  • Alpha-synuclein production in yeast affects the Golgi-transport system and phospholipid biosynthesis.
  • Ypt7 is a Rab GTPase shown to be directly involved in lipid production in yeast.
  • RABs colocalize both the Golgi membranes as well as the contractile vacuole system in the slime mould, Dictyostelium.
  • Intellectual Property patented by Hyasynth Biologicals documents the production of cannabinoids in yeast by utilizing a Dictyostelium discoideum polyketide synthase pathway.

Sources

  1. McCaw EA, Hu H, Gomez GT, Hebb AL, Kelly ME, Denovan-Wright EM. Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington’s disease transgenic mice. Eur J Biochem. 2004;271(23-24):4909-4920.
  2. Giuffrida, Andrea (2017). The Endocannabinoid System || The Endocannabinoid System and Parkinson Disease. , (), 63–81. doi:10.1016/B978-0-12-809666-6.00003-4 
  3. Soper, J.H., Kehm, V., Burd, C.G. et al. Aggregation of α-Synuclein in S. cerevisiae is Associated with Defects in Endosomal Trafficking and Phospholipid Biosynthesis. J Mol Neurosci 43, 391–405 (2011).
  4. Hyasynth Biologicals. WO2018148848. 02/2017.
  5. Maringer K, Yarbrough A, Sims-Lucas S, Saheb E, Jawed S, Bush J. Dictyostelium discoideum RabS and Rab2 colocalize with the Golgi and contractile vacuole system and regulate osmoregulation. J Biosci. 2016;41(2):205-217. doi:10.1007/s12038-016-9610-4
  6. Stroupe C. The yeast vacuolar Rab GTPase Ypt7p has an activity beyond membrane recruitment of the homotypic fusion and protein sorting-Class C Vps complex. Biochem J. 2012;443(1):205-211. doi:10.1042/BJ20110687

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