ChEMS Seminar: Expanding Capabilities for Biochemical Production Using Oleaginous Yeast

Abstract: Biochemical production has been practiced for centuries; however recent advances in genomics and synthetic biology have enabled exploitation of a wide array of microbes engineered to produce an unprecedented number of molecules with greater efficiency. Specifically, these advances are enabled by an increasing catalog of biocatalysts (microorganisms) with properties well suited for certain biochemical production. The engineering challenge is to improve these biocatalysts to perform non-native reactions and to increase productivities and yields to levels of economic viability. Since these biocatalysts are produced by the genes encoded in microbial genomes, genetic engineering tools and a better understanding of cellular metabolism are needed. Our group focuses on oleaginous yeasts that use a variety of feedstocks and are able to naturally accumulate a large amount of lipids. This seminar describes our development of genetic engineering tools for Yarrowia lipolytica and their application to better understanding and engineering of cellular metabolism. We have built promoters that control both the strength and the timing of gene transcription. Whereas there is great complexity in Y. lipolytica promoter, we’ve identified the TATA box as a programmable and modular component of these promoters. Upstream response elements were discovered and engineered to make a strong and tightly regulated fatty acid inducible promoter that can be used to induce gene expression or to sense intracellular fatty acids. To increase the speed of strain engineering, a CRISPR-Cas9 system was developed for efficient genome editing, and compatible standard integration sites were identified. Using these tools, we’ve elucidated a cryptic xylose metabolism pathway and engineered it to grow nearly as fast as it grows on glucose. Continued genetic engineering tool development will provide additional control of cellular metabolism enabling a broader range of products to be developed.

Bio: Mark Blenner is an assistant professor and the Dean’s Professor of Chemical and Biomolecular Engineering at Clemson University. He received his doctorate in chemical engineering from Columbia University in 2009 and completed three years of postdoctoral training as an American Heart Association Postdoctoral Fellow and an NIH NRSA Postdoctoral Fellow at Harvard Medical School and Children’s Hospital Boston. Blenner is an Air Force Office of Scientific Research Young Investigator Awardee and a NASA Early Career Faculty Award winner. His research is focused on developing new synthetic biology capabilites and their application to biochemical synthesis.

Host: Nancy Da Silva