Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis

Abstract

BackgroundGlycolic acid is a C2 hydroxy acid that is a widely used chemical compound. It can be polymerised to produce biodegradable polymers with excellent gas barrier properties. Currently, glycolic acid is produced in a chemical process using fossil resources and toxic chemicals. Biotechnological production of glycolic acid using renewable resources is a desirable alternative.ResultsThe yeasts Saccharomyces cerevisiae and Kluyveromyces lactis are suitable organisms for glycolic acid production since they are acid tolerant and can grow in the presence of up to 50 g l-1 glycolic acid. We engineered S. cerevisiae and K. lactis for glycolic acid production using the reactions of the glyoxylate cycle to produce glyoxylic acid and then reducing it to glycolic acid. The expression of a high affinity glyoxylate reductase alone already led to glycolic acid production. The production was further improved by deleting genes encoding malate synthase and the cytosolic form of isocitrate dehydrogenase. The engineered S. cerevisiae strain produced up to about 1 g l-1 of glycolic acid in a medium containing d-xylose and ethanol. Similar modifications in K. lactis resulted in a much higher glycolic acid titer. In a bioreactor cultivation with d-xylose and ethanol up to 15 g l-1 of glycolic acid was obtained.ConclusionsThis is the first demonstration of engineering yeast to produce glycolic acid. Prior to this work glycolic acid production through the glyoxylate cycle has only been reported in bacteria. The benefit of a yeast host is the possibility for glycolic acid production also at low pH, which was demonstrated in flask cultivations. Production of glycolic acid was first shown in S. cerevisiae. To test whether a Crabtree negative yeast would be better suited for glycolic acid production we engineered K. lactis in the same way and demonstrated it to be a better host for glycolic acid production.

Xylose assimilation enhances the production of isobutanol in engineered Saccharomyces cerevisiae

“…Considering that the isobutanol production pathway in SR8-Iso is compartmentalized in the mitochondria, it is likely that increased mitochondrial biogenesis is a major contributor to the enhanced isobutanol yields from xylose we observe. However, other physiological changes induced by xylose that could divert flux from ethanol to isobutanol production may still be taking place, which would be consistent with several examples where engineered biosynthetic pathways are enhanced by xylose utilization without involving their compartmentalization in mitochondria (S. K. Kim, Jo, Park, Jin, & Seo, 2017;Koivistoinen et al, 2013;Kwak, Kim et al, 2017;Salusjärvi et al, 2017;Turner et al, 2015). Future research to elucidate what physiological changes brought by xylose are responsible for this product biosynthesis enhancement may provide new insights to engineer strains with improved bioconversion of glucose into isobutanol and other nonethanol products.…”

Production of valuable compounds by molds and yeasts

“…124 Engineered S. cerevisiae made only 1 g l − 1 , but engineered K. lactis produced 15 g l − 1 from ethanol plus D-xylose. It is polymerized to polyglycolic acid that is excellent for preparing packaging material.…”

The spoilage yeastZygosaccharomyces bailii: Foe or friend?

“…Yeast‐based fermentations for the production of organic acids starting from cheap carbon sources are well documented in the literature (Ilmen et al ., ; Koivistoinen et al ., ; Valli et al ., ; Xu et al ., ; Zelle et al ., ), often taking advantage of the ability of these cells to sustain adequate growth at stressful but desired conditions. Organic acids represent building blocks for several products (polymers, cosmetics and pharmaceutics) of industrial and commercial interest.…”