Engineering Yarrowia lipolytica to Produce Tailored Chain-Length Fatty Acids and Their Derivatives

Microbial production of value-added chemicals derived from fatty acids is a sustainable alternative to petroleum-derived chemicals and unsustainable lipids from animals and plants. Fatty acids with different carbon chain lengths including short- (<C6), medium- (C6-C12), long- (C14-C20), and very-long- (>C20), with either even or odd number of carbons, have significantly different characteristics and wide applications in energy, material, medicine, and nutrition. Tailoring chain-length specificity of these compounds using metabolic engineering would be of high interest. Yarrowia lipolytica, as an oleaginous yeast, is a superior industrial chassis for the production of tailored chain-length fatty acids and their derivatives due to its hyper-oil-producing capability. In this Review, we cover metabolic engineering approaches that can lead to fatty acid chain length control in this microorganism. These approaches involve the manipulation of the fatty acid synthase, the thioesterase, the β-oxidation pathway, the elongation and desaturation pathway, the polyketide synthase-like polyunsaturated fatty acid synthase pathway, and the odd-chain fatty acids synthesis pathway. Finally, we also discuss alternative strategies that can be used in the future to tailored chain-length control.