(188az) Engineering Yarrowia Lipolytica As a Platform for Production of Plant Secondary Metabolites

Yarrowia lipolytica is an oleaginous yeast that have been substantially engineered for production of oleochemcials and drop-in transportation fuels. It has been recognized as a generally regarded as safe (GRAS) organism for the production of organic acids in the food and nutraceutical industry. The high precursor acetyl-CoA and malonyl-CoA flux along with the versatile carbon-utilization capability places this yeast as a superior host to upgrade low-value carbons into high-value pharmaceuticals and plant natural products (PNPs). Bacteria system in general is less efficient to express the complex gene cluster of plant natural product pathway. Unlike bacteria, yeast has developed spatially separated organelles to partition specialized metabolic functions into distinct cellular compartments. In this talk, we will present strategies to graft the acetyl-CoA/malonyl-CoA pathway toward engineering efficient yeast cell factories to produce complex terpenes and polyketides. We identified pathway limitations and assessed genetic engineering strategies to elevate the level of HMG-CoA, malonyl-CoA and NADPH. This talk will provide a testbed for engineering Y. lipolytica and expanding nature’s capacity to produce complex PNPs with pharmaceutical values for clinical trials and treating emerging diseases.