The advances in creating Crabtree-negative Saccharomyces cerevisiae and the application for chemicals biosynthesis

Saccharomyces cerevisiae is a promising microbial cell factory. However, the overflow metabolism, known as the Crabtree effect, directs the majority of the carbon source toward ethanol production, in many cases, resulting in low yields of other target chemicals and byproducts accumulation. To construct Crabtree-negative S. cerevisiae, the deletion of pyruvate decarboxylases and/or ethanol dehydrogenases is required. However, these modifications compromises the growth of the strains on glucose. This review discusses the metabolic engineering approaches used to eliminate ethanol production, the efforts to alleviate growth defect of Crabtree-negative strains, and the underlying mechanisms of the growth rescue. In addition, it summarizes the applications of Crabtree-negative S. cerevisiae in the synthesis of various chemicals such as lactic acid, 2,3-butanediol, malic acid, succinic acid, isobutanol, and others.