Sustainable production of glutathione from lignocellulose-derived sugars using engineered Saccharomyces cerevisiae

• Published in: Applied microbiology and biotechnology Vol. 103; no. 3; pp. 1243 - 1254
• Main Authors: Kobayashi, Jyumpei, Sasaki, Daisuke, Bamba, Takahiro, Hasunuma, Tomohisa, Kondo, Akihiko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2019; Springer; Springer Nature B.V
• Subjects: Baking yeast; Biomedical and Life Sciences; Bioreactors - microbiology; Biotechnological Products and Process Engineering; Biotechnology; Cell growth; Chemical properties; D-Xylulose Reductase - genetics; Fermentation; Genes; Genetic engineering; Genetic Engineering - methods; Genetically modified organisms; Glucose; Glucose - metabolism; Glutamate-Cysteine Ligase - genetics; Glutathione; Glutathione - biosynthesis; Glutathione Synthase - genetics; Industrial engineering; Life Sciences; Ligases; Lignin - metabolism; Lignocellulose; Manufacturing costs; Manufacturing engineering; Mass production; Microbial Genetics and Genomics; Microbiology; Monosaccharides; Phosphotransferases (Alcohol Group Acceptor) - genetics; Production costs; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sugar; Thiols; Xylitol; Xylitol dehydrogenase; Xylose; Xylose - metabolism; Xylose reductase; Xylulokinase; Yeast; γ-Glutamylcysteine; D-Xylose; Aldose reductase; D-Xylose reductase; Glutathione; Xylitol dehydrogenase; Saccharomyces cerevisiae
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-018-9493-4

Glutathione has diverse physiological functions, and therefore, the demand for it has increased recently. Currently, industrial mass production of glutathione is performed from D-glucose via fermentation by the budding yeast Saccharomyces cerevisiae . However, use of D-glucose often competes with demands for various other industries, leading to high production costs. To affordably produce glutathione, we aimed to produce high amounts of glutathione from D-glucose and D-xylose, which are the main constituents of lignocellulosic biomass pre-treated with acids. Genetically engineered S. cerevisiae strains that can produce high amounts of glutathione and assimilate D-xylose were constructed and cultured in media containing D-xylose. Among these recombinant strains, a S. cerevisiae GCI ( XR / XDH / XK ) strain over-expressing γ-glutamylcysteine synthetase, glutathione synthetase, D-xylose reductase, xylitol dehydrogenase, and xylulokinase genes successfully consumed D-xylose in the medium and produced the highest amount of glutathione. When strains were grown in media containing D-glucose and D-xylose, the GCI ( XR / XDH / XK ) strain showed 4.6-fold higher volumetric glutathione production (mg/L-broth), 2.2-fold higher glutathione content (%), and 2.1-fold higher cell growth (g-cell/L-broth) than the vector control strain of YPH499 (Vector). Furthermore, when recombinant S. cerevisiae strains were grown in medium containing fermentation inhibitory materials, the GCI ( XR / XDH / XK ) strain produced 5.8- and higher volumetric glutathione, 2.6-fold higher intracellular glutathione, and 2.9-fold higher cell growth than the vector control YPH499 (Vector) strain. The gradual sugar consumption by recombinant S. cerevisiae strains in medium containing D-glucose and D-xylose leads to high yields of glutathione. These results indicate the potential for glutathione production from lignocellulosic materials.