Global Discovery Chemistry
Cambridge, Massachusetts, United States
In the Synthetic Biology group, we produce therapeutically-relevant natural products and natural product analogs in heterologous microbial systems, including S. cerevisiae, E. coli, and Streptomyces lab strains. Natural products are made by bacteria, fungi, and plants and perform useful biological functions for their producer organisms. In many cases, these compounds have also been shown to possess potent human therapeutic functions. The ability to isolate and manipulate these natural products could expand potential drug leads.
An important set of natural products that has been difficult to access are those produced by plants. We want to understand the genetic and enzymatic basis of plant natural product biosynthesis to transfer these biosynthetic pathways and compound production to a genetically tractable eukaryotic system such as S. cerevisiae (budding yeast). To accomplish this goal, we will (1) develop a system to extract relevant genomic and RNA expression data and compound production information from plant tissues to elucidate biosynthetic pathways, and (2) transfer relevant genetic information to yeast strains to express plant biosynthetic pathway genes and produce the corresponding natural products. Once we understand these biosynthetic pathways, we will use synthetic biology techniques to modify the pathways to generate natural product analogs in yeast and test their biological activities as compared to the parent compounds. In this way, we hope to generate novel compounds that have unique biological activities but are difficult to access using synthetic chemistry or tissue extraction techniques.
Efficient ethanol production from brown macroalgae sugars by a synthetic yeast platform.
Enquist-Newman M*, Faust AM*, Bravo DD*, Santos CN, Raisner RM, Hanel A, Sarvabhowman P, Le C, Regitsky DD, Cooper SR, Peereboom L, Clark A, Martinez Y, Goldsmith J, Cho MY, Donohoue PD, Luo L, Lamberson B, Tamrakar P, Kim EJ, Villari JL, Gill A, Tripathi SA, Karamchedu P, Paredes CJ, Rajgarhia V, Kotlar HK, Bailey RB, Miller DJ, Ohler NL, Swimmer C, Yoshikuni Y.
Nature. 2014 Jan 9; 505(7482):239-43.
The FEAR protein Slk19 restricts Cdc14 phosphatase to the nucleus until the end of anaphase, regulating its participation in mitotic exit in Saccharomyces cerevisiae.
Faust AM, Wong CC, Yates JR 3rd, Drubin DG, Barnes G.
PLoS One. 2013 Sep 10; 8(9):e73194.
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