Team:ULaval

What is Saccharomyces cerevisiae ?
Saccharomyces cerevisiae is a single-celled microorganism commonly known as the brewer's yeast. This yeast is a facultative anaerobe which means that it has both the ability to grow using oxygen via cellular respiration as well as to undergo fermentation in the absence of oxygen.1

What is adrenaline ?
Adrenaline is a hormone secreted by the medulla of the adrenal glands. Its production is increased in response to fear and stress in order to prepare the body to react promptly. It causes a raise in blood pressure, vasodilation in the skeletal muscles, bronchodilation and pupil dilation. 2

What are the uses of yeast ?


S.cerevisiae is the Brewer’s yeast!
Indeed, it is the principal microorganism
responsible for the fermentation process
during brewing. It is also used in baking to
leaven bread, in winemaking to ferment the
beverage and in various scientific
research as a model.1, 3
What is the use of adrenaline ?


Adrenaline
is used as an
emergency treatment
during life-threatening
anaphylactic reactions
and cardiac arrest. It
may also be used
to control minor
bleeding and
asthma.4



So, what's the problem ?
Beers are doing just fine. However, the current chemical manufacturing processes to produce adrenaline struggle to keep up with the demand, often leading to shortages of potentially life-saving medicine5. In addition, the chemical synthesis of adrenaline involves the use of toxic and dangerous substances6.

Our Solution
The union of yeast and the adrenaline enzymatic machinery.


We intend to use S. cerevisiae to produce adrenaline that can be purified and stored.



Bonus !
As the enzymatic pathway also produces metabolic intermediates of biomedical interest, we intend to create three strains of Saccharomyces cerevisiae producing dopamine, noradrenaline or adrenaline2.


Our approach
We designed a two-plasmid system which harbors synthetic human cDNAs encoding the adrenaline enzymatic pathway. We explored how the insertion of this plasmid system into a Saccharomyces cerevisiae strain engineered to overproduce L-tyrosine can be used for the biosynthesis of adrenaline7. The metabolic intermediates will be produced based on plasmid combination. We are also developing an optimized protocol to harvest purified products from raw cell culture.


References
1. Dashko, S., Zhou, N., Compagno, C. & Piškur, J., 2014. Why, when, and how did yeast evolve alcoholic fermentation?. FEMS Yeast Research, 14(6), pp. 826-832
2. Pocock, G., Richards, C. D. & Richards, D. A., 2013. Human Physiology. Fourth ed. Oxford: Oxford University Press.
3. Willey, J., Sherwood, L. & Woolverton, C., 2011. Prescott's Microbiology. 8th ed. New York: McGraw-Hill Science/Engineering/Math.
4. Burchum, J. R. & Rosenthal, L. D., 2016. Lehne's Pharmacology for Nursing Care. 9th ed. USA: Elsevier.
5. Yang, C. et al., 2016. Current Situation, Determinants, and Solutions to Drug Shortages in Shaanxi Province, China: A Qualitative Study. Plos One, 11(10).
6. Sriram, D. & Yogeeswari, P., 2010. Medicinal Chemistry. 2nd ed. India: Pearsons.
7. Gold, N. D. et al., 2015. Metabolic engineering of a tyrosine-overproducing yeast platform using targetedmetabolomics. Microbial Cell Factories, 14(73).
igem@bcm.ulaval.ca