Portable Progesterone Production in Yeast: PoPPY
This year’s UCSC iGEM team seeks to address the global lack of family planning services. Through our research, we found that many women around the globe cannot access contraceptives. The luxury to choose when, and if, to start a family directly affects one’s ability to pursue many life goals. This could be an education, sports, a career, or much more. Our hope is to localize contraception production and increase availability in resource constrained communities. Progesterone, a hormone naturally produced by women, can be used to suppress ovulation and act as a form of contraception. The yeast Yarrowia lipolytica is an organism that is considered generally recognized as safe (GRAS) by the Food and Drug Administration [2,3]. It has an advanced genetic toolbox and can also be easily grown in varied environments[4,5]. We will engineer a strain of Y. lipolytica to produce progesterone with the goal of creating a product that can be used within the home to grow one’s own contraceptives.
We found a common theme for women who live far from contraceptive providers: they travel a great distance to find that “the provider has [run] out” or to “find no doctors” to administer injectable forms.
Women with limited choices for contraception may turn to dangerous options. We want to help increase the availability of safe forms of contraception. Our progesterone-producing Y. lipolytica will survive on animal milk . Animals that produce milk are widely available around the world. This will allow women anywhere to grow their own birth control.
Rumors were another common theme in responses to our outreach. Some are extreme; for example, we heard that people believe that birth control causes women to “produce lame, blind children”. Part of this stigma may lie in how modern birth control “pills” are made in factories with chemical compounds. Our team will expand communities' education about modern birth control methods and alleviate fears by addressing rumors.
We found five genes, from three different organisms, that complete the metabolic pathway to progesterone biosynthesis.
In each experiment, we will insert the assembled genes into the host genome.
We will engineer these genes into the yeast Yarrowia lipolytica using three parallel experiments. Each will first use genetic cloning to assemble to genes together into one plasmid.
In each experiment, we will then insert the assembled genes into the host genome.
The cells will then have the genes required to biosynthesize progesterone. We will quantify the amount of progesterone produced using a riboswitch we have engineered to create a reliable dosage for consumers.
The three ways we will insert the genes
- Gibson Assembly to create the gene cassette, and homologous recombination to insert the cassette into the Y. lipolytica genome.
- Yeast-mediated cloning in Saccharomyces cerevisiae as a model organism to create the gene cassette, and Cre-Lox recombination to insert the cassette into the Y. lipolytica genome.
- Yeast-mediated cloning to create the gene cassette and Cre-Lox recombination to insert the cassette, both within Y. lipolytica.
- We will insert five genes to complete the progesterone pathway in Y. lipolytica, confirm that the strain can survive on dairy and produce progesterone, and quantify the progesterone produced to create a reliable dosage.
- Long term, we want to make birth control affordable and sustainable for women in developing countries. We want to raise awareness about contraceptives by correcting common misconceptions about birth control and providing women with a safe option for birth control.
- Finally, we plan to aid women in low-resource areas by collaborating with powerful organizations like Family Planning 2020, the Brighter Brains Institute, and the specific women’s groups in Uganda who have told us about their experiences with contraceptives.
- Apgar, B. S., and Greenberg, G. M. (2000). Using Progestins in Clinical Practice. AFP 62, 1839–1846.
- U.S. Food & Drug Administration (2011). GRAS Notices - GRN No. 355.
- Groenewald, M., Boekhout, T., Neuvéglise, C., Gaillardin, C., Dijick, P. W. M. v., and Wyss, M. (2014). Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential. Critical Reviews in Microbiology 40, 187-206.
- Roostita, R. and Fleet, G.H. (1996). Growth of yeasts in milk and associated changes to milk composition. International Journal of Food Microbiology 31, 205-219.
- Fabiszewska, A. U., Kotryba, D., and Nowak, D. (2015). Assortment of carbon sources in medium for Yarrowia lipolytica lipase production: A statistical approach Annals of Microbiology 65, 1495-1503.