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

If you buy a product like a car tire or a light switch, chances are it’s been stress tested. That is, a test simulates years of use to ensure a design can withstand any conditions it might be subjected to. Likewise, a cannabis plant can consist of disease-resistant genetics that can yield good profiles. For example, can a disease that affects the biosynthesis of cannabinoids serve as a stress test for yeast engineered to produce THC or methyl-CBD?

Neurodegenerative diseases and cannabinoids

A mutated human gene causes Huntington’s disease. In addition, the early stages of the neurodegenerative disease usually involve severe CB1 receptor depletion. (1) This is why HD helps us understand the endocannabinoid system. However, the origins of CB receptors are unrelated to the biosynthesis of cannabinoids. Therefore, infecting a yeast with HD may not be a good stress test for THC production.

However, Parkinson’s disease also affects the ECS. (2) Genes commonly studied in artificial yeast models produce proteins responsible for PD. One study found effects on certain cell functions. (3) And one of those functions directly affects a novel cannabinoid biosynthetic pathway patented by Hyasynth Biologicals. (4, 5)

Infectious proteins and cell lipids

Transport networks enable the movement of lipids — including endocannabinoids — within cells. However, proteins that cause Parkinson’s disease also disrupt cellular switches and critical lipid transit systems. (3, 5, 6) Although the process cannot be recommended for production due to potential public health risks. Infecting yeast with Parkinson’s disease by manipulating them to produce alpha-synuclein could therefore act as a stress test for cannabinoid biosynthesis.

However, scientific experiments often work with yeast models of Parkinson’s disease. (3) The concern of the concept is of course still containment. On a research and development scale, this does not violate normal procedures. When it comes to production, however, the cannabinoid industry appears to be steeped in regulation. But are new processes potentially employed in cannabinoid biosynthesis really being considered by the same legislators that allow the use of chloropicrin?

Let us know in the comments if you think cannabinoid biosynthesis assays should be better established in a yeast or bacterial medium.

Show your work

• In yeast, alpha-synuclein (the protein that causes Parkinson’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 that has been shown to be directly involved in lipid production in yeast.
• RABs colocalize both the Golgi membranes and the contractile vacuole system in the slime mold Dictyostelium.
• Hyasynth Biologicals’ patented intellectual property documents the production of cannabinoids in yeast using a polyketide synthase pathway from Dictyostelium discoideum.

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 transgenic HD mice. Eur. J. Biochem. 2004;271(23-24):4909-4920.
2. Giuffrida, Andrea (2017). The endocannabinoid system || The endocannabinoid system and Parkinson’s disease. , (), 63–81. doi:10.1016/B978-0-12-809666-6.00003-4
3. Soper, JH, Kehm, V, Burd, CG et al. Aggregation of α-synuclein in S. cerevisiae is associated with defects in endosomal transport 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 systems 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 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