The oleaginous yeast Yarrowia lipolytica can accumulate lipids at near-theoretical maximum yields from diverse carbon sources, including biomass-derived sugars and waste-derived acetate. Under nitrogen-limited conditions, this organism's highly efficient lipogenesis has enabled lipid titers exceeding 100 g/L and production rates above 1 g/L/h in fed-batch fermentation. However, maximum conversion yields remain constrained by the inherent electron content of oxidized substrates: 0.27 g/g from glucose and 0.16 g/g from acetate, reflecting the fundamental mismatch between the oxidation state of these carbon sources and the reduced nature of lipids.
This presentation will summarize a decade of engineering efforts in the Stephanopoulos laboratory to enhance Y. lipolytica for high-yield lipid production from various substrates. I will present our current approach to surpass theoretical maximum yields by supplying additional electrons ultimately derived from carbon-free electrical energy. Through combinatorial strategies encompassing carbon-conserved metabolic pathway engineering and efficient energy transduction systems, we have developed a strain capable of decoupled carbon and energy metabolism. This platform is enabling us to achieve fully carbon-conserved conversion of oxidized substrates to lipids at yields that exceed the theoretical maximum based on substrate carbon content alone.
