The Effect of Deletion of the NDE1 Gene on Properties of the Yeast Schizosaccharomyces pombe Producing L-Lactic Acid

Abstract

Based on acidophilic strain Schizosaccharomyces pombe, L-lactic acid producing strains with deletion of the NDE1 gene encoding NADH dehydrogenase, presumably regulating the cytosolic NADH/NAD+ balance in yeast, were constructed. When the genome of previously obtained producer strains is saturated with heterologous L-LDH genes encoding L-lactate dehydrogenase, culture growth worsens and glucose consumption slows down. An increase in the dose of L-LDH genes does not always lead to an increase in biosynthesis of the target product. Perhaps the limiting factor in the biosynthesis of lactic acid is the lack of cytosolic NADH oxidized to NAD+ by NADH dehydrogenase encoded by the NDE1 gene. The S. pombe strain with deletion of the NDE1 gene and an additional copy of the L-LDH gene surpasses the parent strain in growth, glucose consumption, and lactic acid biosynthesis (139 g/L, which is 28% more, final pH 3.2). This study will provide a better understanding of the underlying cellular processes in the yeast S. pombe and use the results obtained for the design of highly productive strains producing lactic acid.