Recent Advances in Natural Product Biosynthesis and Yield Improvement Strategies Using Yarrowia lipolytica

Microorganisms are increasingly being used for the industrial production of raw materials for food, chemical products and pharmaceuticals. The unconventional yeast Yarrowia lipolytica has a rising profile as a platform for industrial biotechnology. It has attractive physiological and metabolic properties, including high terpene and lipid production, high tolerance to complex environments, and amenability to genetic modification. Y. lipolytica naturally produces sufficient levels of cytosolic acetyl-CoA and malonyl-CoA to achieve lipid accumulation. Engineering biology methods allow transformation of these native metabolites into synthetic precursors for high-value compounds such as terpenes and flavonoids. Gene-editing, expression, and regulation tools have been developed for Y. lipolytica, facilitating improvement in bio-manufacturing yields for this chassis. This review summarizes natural product yields in Y. lipolytica and strategies for improving productivity. We highlight morphological engineering, metabolic engineering, and adaptive laboratory evolution as key strategies that can be used to improve the future yield, productivity and controllability of target molecules for Y. lipolytica engineering.