(280a) Engineering Yarrowia lipolytica for the Production of Isoprenoids

Isoprenoids comprise one of the largest and highly diverse class of compounds with remarkable biomedical and industrial applications. The low yields of isoprenoids from natural sources are not sufficient to satisfy the high demand of these important compounds. To tackle this challenge, metabolic engineering has emerged as an alternative strategy for reconstructing heterologous pathways in genetically tractable hosts. The hydrophobic nature of most isoprenoids is intrinsically incompatible with the aqueous intracellular microenvironment of conventional organisms, such as Saccharomyces cerevisiae and Escherichia coli. Taking into account the limitations of the aforementioned hosts, the oleaginous yeast Yarrowia lipolytica represents an attractive alternative expression platform for sustainable production of hydrophobic molecules. This is due to its ability to accumulate and store large amounts of lipids and fatty acids, rendering the intracellular microenvironment primarily hydrophobic. Hence, the lipid-producing host Y. lipolytica holds great potential for the production of a wide variety of commercially relevant and fat-soluble isoprenoids. Accordingly, when the long-chain lycopene was targeted as a model isoprenoid compound, we observed a correlation between the intracellular lipid content and the amount of lycopene. This approach in conjunction with metabolic engineering attempts to improve isoprenoid precursor availability further boosted lycopene titers. The increased capacity of Y. lipolytica for isoprenoid production will be demonstrated by providing examples of synthesis of further isoprenoid products under varying conditions of lipid accumulation in this host.