Replacement of a metabolic pathway for large-scale production of lactic acid from engineered yeasts

Interest in the production of L-(+)-lactic acid is presently growing in rel ation to its applications in the synthesis of biodegradable polymer materia ls. With the aim of obtaining efficient production and high productivity, w e introduced the bovine L-lactate dehydrogenase gene (LDH) into a wild-type Kluyveromyces lactis yeast strain. The observed lactic acid production was not satisfactory due to the continued coproduction of ethanol. A further r estructuring of the cellular metabolism was obtained by introducing the LDH gene into a K. lactis strain in which the unique pyruvate decarboxylase ge ne had been deleted. With this modified strain, in which lactic fermentatio n substituted completely for the pathway leading to the production of ethan ol, we obtained concentrations, productivities, and yields of lactic acid a s high as 109 g liter(-1), 0.91 g liter(-1) h(-1), and 1.19 mol per mole of glucose consumed, respectively. The organic acid was also produced at pH l evels lower than those usual for bacterial processes.