Project 15. High throughput platform for improving metrics and expanding diversity of secondary metabolites and proteins produced by yeast biofactories
Many secondary metabolites and proteins in nature have high value because of their therapeutic, nutraceutical, agricultural, or even recreational potentials. The harvest of such compounds from their original producers is not sustainable both environmentally, economically, and politically. Arguably, the most ideal way to produce secondary metabolites or proteins of commercial interest is through conversion of renewable carbon sources, e.g. glucose, by microorganisms that grow relatively fast, in metrics (i.e., titer, rate, yield) that are relevant to industrial scale. Specifically given that many of such secondary metabolites and proteins are produced by plants and fungi, during which
compartmentalization is critical, yeast is the preferred microbial host for heterologous secondary metabolites production relative to bacteria.
The focus of this PhD project will be on the making of a library of ~100 chaperones and screen it to find member(s) that might improve folding and function of several test proteins. Contingent upon such outcome, alternatively a library of ~100 CYP/CYP reductases and/or ~100 GTs will be built and screened to find member(s) that might complete the missing step in several model biosynthesis pathways and/or alleviate toxicity of several model secondary metabolites, respectively.
Read more about Eukaryotic Molecular Cell Biology.
Previously in the lab of Dr. Brian Pfleger at the University of Wisconsin, Madison, USA, I developed a set of synthetic biology tools to facilitate reliable episomal gene expression in Pseudomonas putida KT2440. This generally recognized as safe (GRAS)-certified organism has recently received great attention from wider metabolic engineering community due to its ability to stand various xenobiotics (including antibiotics and various organic solvents), ability to express GC-rich genes typical of many actinobacteria and myxobacteria’s secondary metabolites gene clusters, and ability to generate huge amount of NADPH required in many biosynthesis reactions. Besides, I also developed synthetic consumption pathway in that organism to facilitate metabolic engineering of gamma-valerolactone, a product of a chemically effective lignocellulose breakdown process, into various useful chemicals.
Additionally during my time in the 2015 Synthetic Biology summer course at Cold Spring Harbor Laboratory, NY, USA, I studied the role of each gene in Escherichia coli chemotaxis circuitry using CRISPR interference technology under the supervision of Dr. Stanley Qi (Stanford University), and engineered Sachharomyces cerevisiae-based whole-cell biosensor for detection of various advanced biofuel molecules under the supervision of Dr. Pamela Peralta-Yahya (Georgia Institute of Technology).