Advanced Strategies for the Synthesis of Terpenoids in Yarrowia lipolytica.

Terpenoids are an important class of secondary metabolites that play an important role in food, agriculture, and other fields. Microorganisms are rapidly emerging as a promising source for the production of terpenoids. As an oleaginous yeast, Yarrowia lipolytica contains a high lipid content which indicates that it must produce high amounts of acetyl-CoA, a necessary precursor for the biosynthesis of terpenoids. Y. lipolytica has a complete eukaryotic mevalonic acid (MVA) pathway but it has not yet seen commercial use due to its low productivity. Several metabolic engineering strategies have been developed to improve the terpenoids production of Y. lipolytica, including developing the orthogonal pathway for terpenoid synthesis, increasing the catalytic efficiency of terpenoids synthases, enhancing the supply of acetyl-CoA and NADPH, expressing rate-limiting genes, and modifying the branched pathway. Moreover, most of the acetyl-CoA is used to produce lipid, so it is an effective strategy to strike a balance of precursor distribution by rewiring the lipid biosynthesis pathway. Lastly, the latest developed non-homologous end-joining strategy for improving terpenoid production is introduced. This review summarizes the status and metabolic engineering strategies of terpenoids biosynthesis in Y. lipolytica and proposes new insights to move the field forward.