Team:Vanderbilt

Our Idea:

Our Approach:

Long before the advent of modern science, it was recognized that certain plants are capable of producing compounds of immense value. From a single class of molecule, the terpenoids, come properties including agents with therapeutic qualities against maladies ranging from cancer to infection, antimicrobials, natural pesticides, rich flavorants, and fragrant scents¹. However, the utilization of these remarkable compounds has been severely hindered by their rarity in nature: many are found in only a small number of species and produced at levels measured in parts per million². Synthetic biology offers an opportunity to resolve this problem, by applying metabolic engineering in order to create cellular factories. Our project seeks to use the ideas of synthetic biology to develop a commercially viable strategy for the efficient production of a wide range of terpenoids.

We believe that common brewer's yeast, or Saccharomyces cerevisiae , is an excellent platform for engineering terpenoid biosynthetic pathways. The mevalonic acid pathway endogenous to yeast produces the key isoprenoid intermediates that are the precursors to virtually all terpenoid biosynthesis³. Genes encoding plant synthases can then be recombinantly expressed in yeast cells, which then take that isoprenoid substrate and convert it through one or more steps into the final terpenoid product. A specially designed biobrick shuttle vector developed by our team should make the process convenient and reliable, by allowing us to first amplify plasmids containing our gene of interest in E. coli and permitting the integration of synthase genes directly into the yeast genome through homologous recombination. A carefully-refined protocol is expected to further improve product yield, by extracting genetic sequences directly from plant genomic DNA and mating cells to form diploid transformants. Combined, our approach promises to be an effective manufacturing platform for these precious (and sweet-smelling) compounds.

References

1. Aharoni A, Jongsma MA, Bouwmeester HJ. Volatile science? Metabolic engineering of terpenoids in plants. Trends Plant Science 2005;10(12):594-602.
2. Ajikumar PK, Tyo K, Carlsen S, Mucha O, Phon TH, Stephanopoulos G. Terpenoids: opportunities for biosynthesis of natural product drugs using engineered microorganisms. Molecular Pharmaceutics 2008;5(2):167-90.
3. Farhi M, Marhevka E, Masci T, Marcos E, Eyal Y, Ovadis M, Abeliovich H, Vainstein A. Harnessing yeast subcellular compartments for the production of plant terpenoids. Metabolic Engineering 2011;13(5):474-81.