Replacement of a Metabolic Pathway for Large-Scale Production of Lactic Acid from Engineered Yeasts

<jats:title>ABSTRACT</jats:title> <jats:p> Interest in the production of <jats:sc>l</jats:sc> -(+)-lactic acid is presently growing in relation to its applications in the synthesis of biodegradable polymer materials. With the aim of obtaining efficient production and high productivity, we introduced the bovine <jats:sc>l</jats:sc> -lactate dehydrogenase gene ( <jats:italic>LDH</jats:italic> ) into a wild-type <jats:italic>Kluyveromyces lactis</jats:italic> yeast strain. The observed lactic acid production was not satisfactory due to the continued coproduction of ethanol. A further restructuring of the cellular metabolism was obtained by introducing the <jats:italic>LDH</jats:italic> gene into a <jats:italic>K. lactis</jats:italic> strain in which the unique pyruvate decarboxylase gene had been deleted. With this modified strain, in which lactic fermentation substituted completely for the pathway leading to the production of ethanol, we obtained concentrations, productivities, and yields of lactic acid as high as 109 g liter <jats:sup>−1</jats:sup> , 0.91 g liter <jats:sup>−1</jats:sup> h <jats:sup>−1</jats:sup> , and 1.19 mol per mole of glucose consumed, respectively. The organic acid was also produced at pH levels lower than those usual for bacterial processes. </jats:p>