α-Ketoglutarate (α-KG) is an important intermediate in the tricarboxylic acid (TCA) cycle and has an important role in the regulation of the balance between carbon and nitrogen metabolism in most microorganisms. In previous research, a thiamine-auxotrophic yeast for α-KG overproduction was screened and named as Yarrowia lipolytica WSH-Z06. To enhance α-KG production and reduce by-product (mainly pyruvate) accumulation, the cofactor metabolism was regulated to redistribute the carbon flux from pyruvate to α-KG. The acetyl-CoA synthetase gene, ACS1, from Saccharomyces cerevisiae and the ATP-citrate lyase gene, ACL, from Mus musculus were expressed to regulate the acetyl-CoA metabolism in Y. lipolytica WSH-Z06. The resultant strains were designated as Y. lipolytica-ACS1 and Y. lipolytica-ACL, respectively. Both of the ACS1 and ACL genes could increase the level of acetyl-CoA and enhance the α-KG production. In a 3-L jar fermenter, the highest yield of α-KG in Y. lipolytica-ACL reached up to 56.5 g L(-1) with an obvious decrease of pyruvate accumulation from 35.1 g L(-1) to 20.2 g L(-1). This study demonstrated that enhancing the acetyl-CoA availability could effectively increase the α-KG production in Y. lipolytica.

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Journal Article | Research Support, Non-U.S. Gov't

Authors

Zhou J, Yin X, Madzak C, Du G, Chen J

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