Exploring succinic acid production by engineered Yarrowia lipolytica strains using glucose at low pH

Succinic acid is an important platform chemical that can be used to produce a broad range of compounds with extensive applications. By applying rational metabolic engineering, we had previously developed a series of innovative succinic acid-producing Yarrowia lipolytica strains that could produce succinic acid effectively using glycerol. In the present study, glucose was used for succinic acid production by these engineered strains, without pH control. Strain PGC11505, in which the gene (YlACH1) of acetyl-CoA hydrolase corresponding for acetic acid overflow was deleted, exhibited the ability to utilize glucose for succinic acid production efficiently. Strain PGC202, with a strengthened reductive carboxylation and oxidative tricarboxylic acid cycle by overexpression of ScPCK and endogenous YlSCS2, yielded 23.8 g/L succinic acid. After fermentation optimization, the succinic acid titer reached to 32.6 g/L in flask cultures. In a bench-top fermenter, this strain produced 53.6 g/L succinic acid with a yield of 0.61 g/g-glucose without pH control. In conclusion, through rational metabolic engineering of Y. lipolytica, we have successfully achieved the high-yield production of succinic acid using glucose as the sole carbon source under natural low pH condition. This new Y. lipolytica strain would be highly useful in industrial processes for the production of succinic acid using low-cost glucose.