Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries

Hong, Kuk-Ki; Nielsen, Jens

doi:10.1007/s00018-012-0945-1

Cited by 392 publications

(282 citation statements)

References 103 publications

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“…In both cases, xylulose is then phosphorylated by an endogenous or heterologous xylulokinase (XKS) and channeled through the nonoxidative branch of the pentose phosphate pathway (PPP) into glycolysis. The usual fermentation product of S. cerevisiae is ethanol, but yeast research also strives to produce other components, like advanced biofuels and chemicals (6)(7)(8).…”

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confidence: 99%

Engineering of yeast hexose transporters to transport d -xylose without inhibition by d -glucose

Farwick

Bruder

Schadeweg

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

269

347

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All known D-xylose transporters are competitively inhibited by D-glucose, which is one of the major reasons hampering simultaneous fermentation of D-glucose and D-xylose, two primary sugars present in lignocellulosic biomass. We have set up a yeast growthbased screening system for mutant D-xylose transporters that are insensitive to the presence of D-glucose. All of the identified variants had a mutation at either a conserved asparagine residue in transmembrane helix 8 or a threonine residue in transmembrane helix 5. According to a homology model of the yeast hexose transporter Gal2 deduced from the crystal structure of the D-xylose transporter XylE from Escherichia coli, both residues are found in the same region of the protein and are positioned slightly to the extracellular side of the central sugar-binding pocket. Therefore, it is likely that alterations sterically prevent D-glucose but not D-xylose from entering the pocket. In contrast, changing amino acids that are supposed to directly interact with the C6 hydroxymethyl group of D-glucose negatively affected transport of both D-glucose and D-xylose. Determination of kinetic properties of the mutant transporters revealed that Gal2-N376F had the highest affinity for D-xylose, along with a moderate transport velocity, and had completely lost the ability to transport hexoses. These transporter versions should prove valuable for glucose-xylose cofermentation in lignocellulosic hydrolysates by Saccharomyces cerevisiae and other biotechnologically relevant organisms. Moreover, our data contribute to the mechanistic understanding of sugar transport because the decisive role of the conserved asparagine residue for determining sugar specificity has not been recognized before.xylose transport | major facilitator superfamily | transporter engineering | pentose metabolism | HXT

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mentioning

confidence: 99%

Engineering of yeast hexose transporters to transport d -xylose without inhibition by d -glucose

Farwick

Bruder

Schadeweg

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

269

347

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“…2). 4 The Pdc-negative strain MK5316 must acquire the enhanced ability to metabolize mannitol, e.g., through adaptive evolution, as in the case of TAM.…”

Section: Resultsmentioning

confidence: 99%

“…[1][2][3] The budding yeast Saccharomyces cerevisiae is a key cell factory that is used for production of a wide range of industrial products. 4 However, S. cerevisiae including the S288C reference strain is generally thought to be unable to assimilate mannitol for growth. 5 However, we 6 and Enquist-Newman et al 7 have recently succeeded in producing S. cerevisiae that can utilize mannitol, thus opening a new way to produce valuable compounds from mannitol.…”

Section: Introductionmentioning

confidence: 99%

Production of pyruvate from mannitol by mannitol-assimilating pyruvate decarboxylase-negative Saccharomyces cerevisiae

et al. 2015

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Mannitol is contained in brown macroalgae up to 33% (w/w, dry weight), and thus is a promising carbon source for white biotechnology. However, Saccharomyces cerevisiae, a key cell factory, is generally regarded to be unable to assimilate mannitol for growth. We have recently succeeded in producing S. cerevisiae that can assimilate mannitol through spontaneous mutations of Tup1-Cyc8, each of which constitutes a general corepressor complex. In this study, we demonstrate production of pyruvate from mannitol using this mannitol-assimilating S. cerevisiae through deletions of all 3 pyruvate decarboxylase genes. The resultant mannitol-assimilating pyruvate decarboxylase-negative strain produced 0.86 g/L pyruvate without use of acetate after cultivation for 4 days, with an overall yield of 0.77 g of pyruvate per g of mannitol (the theoretical yield was 79%). Although acetate was not needed for growth of this strain in mannitol-containing medium, addition of acetate had a significant beneficial effect on production of pyruvate. This is the first report of production of a valuable compound (other than ethanol) from mannitol using S. cerevisiae, and is an initial platform from which the productivity of pyruvate from mannitol can be improved.

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“…Natural and engineered yeast cell factories are today extensively used for commercial productions [16]. Based upon their innate metabolic abilities, yeasts have been employed since several decades for large-scale production of different natural compounds.…”

Section: Introductionmentioning

confidence: 99%

Physiological Effects of GLT1 Modulation in Saccharomyces cerevisiae Strains Growing on Different Nitrogen Sources

Brambilla¹,

Adamo²,

Frascotti³

et al. 2016

Journal of Microbiology and Biotechnology

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Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries

Cited by 392 publications

References 103 publications

Engineering of yeast hexose transporters to transport d -xylose without inhibition by d -glucose

Engineering of yeast hexose transporters to transport d -xylose without inhibition by d -glucose

Production of pyruvate from mannitol by mannitol-assimilating pyruvate decarboxylase-negative Saccharomyces cerevisiae

Physiological Effects of GLT1 Modulation in Saccharomyces cerevisiae Strains Growing on Different Nitrogen Sources

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