The enzymatic transformation of uridine diphosphate glucose into a galactose derivative

Leloir, Luis F.

doi:10.1016/0003-9861(51)90096-3

Cited by 407 publications

(140 citation statements)

References 6 publications

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“…Galactose, another sugar that can be fermented by S. cerevisiae, is first taken up by a dedicated member of the HXT family, the galactose permease Gal2p, and subsequently converted into glucose-6-phosphate via the Leloir pathway (Leloir 1951;Melcher 1997) ( Fig. 2).…”

Section: Fermentation Of Hexoses By Saccharomyces Cerevisiaementioning

confidence: 99%

Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status

Maris

Abbott

Bellissimi

et al. 2006

Antonie van Leeuwenhoek

432

276

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Fuel ethanol production from plant biomass hydrolysates by Saccharomyces cerevisiae is of great economic and environmental significance. This paper reviews the current status with respect to alcoholic fermentation of the main plant biomass-derived monosaccharides by this yeast. Wild-type S. cerevisiae strains readily ferment glucose, mannose and fructose via the Embden-Meyerhof pathway of glycolysis, while galactose is fermented via the Leloir pathway. Construction of yeast strains that efficiently convert other potentially fermentable substrates in plant biomass hydrolysates into ethanol is a major challenge in metabolic engineering. The most abundant of these compounds is xylose. Recent metabolic and evolutionary engineering studies on S. cerevisiae strains that express a fungal xylose isomerase have enabled the rapid and efficient anaerobic fermentation of this pentose.L-Arabinose fermentation, based on the expression of a prokaryotic pathway in S. cerevisiae, has also been established, but needs further optimization before it can be considered for industrial implementation. In addition to these already investigated strategies, possible approaches for metabolic engineering of galacturonic acid and rhamnose fermentation by S. cerevisiae are discussed. An emerging and major challenge is to achieve the rapid transition from proof-of-principle experiments under 'academic' conditions (synthetic media, single substrates or simple substrate mixtures, absence of toxic inhibitors) towards efficient conversion of complex industrial substrate mixtures that contain synergistically acting inhibitors.

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Section: Fermentation Of Hexoses By Saccharomyces Cerevisiaementioning

confidence: 99%

Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status

Maris

Abbott

Bellissimi

et al. 2006

Antonie van Leeuwenhoek

432

276

View full text Add to dashboard Cite

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“…[1][2][3][4][5] GALT is the second enzyme in the evolutionarily conserved galactose metabolic pathway, and facilitates the simultaneous conversion of uridine diphosphoglucose and galactose-1 phosphate (gal-1P) to uridine diphosphogalactose (UDP-galactose) and glucose-1 phosphate (Supplementary Figure 1). 6 GALT deficiency leads to accumulation of gal-1P, deficiency of UDP-galactose and other metabolic derangements. 7,8 If untreated, Classic Galactosemia can be lethal for the affected newborns.…”

Section: Introductionmentioning

confidence: 99%

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

et al. 2014

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The first GalT gene knockout (KO) mouse model for Classic Galactosemia (OMIM 230400) accumulated some galactose and its metabolites upon galactose challenge, but was seemingly fertile and symptom free. Here we constructed a new GalT genetrapped mouse model by injecting GalT gene-trapped mouse embryonic stem cells into blastocysts, which were later implanted into pseudo-pregnant females. High percentage GalT gene-trapped chimera obtained were used to generate heterozygous and subsequently, homozygous GalT gene-trapped mice. Biochemical assays confirmed total absence of galactose-1 phosphate uridylyltransferase (GALT) activity in the homozygotes. Although the homozygous GalT gene-trapped females could conceive and give birth when fed with normal chow, they had smaller litter size (P ¼ 0.02) and longer time-to-pregnancy (P ¼ 0.013) than their wild-type littermates. Follicle-stimulating hormone levels of the mutant female mice were not significantly different from the age-matched, wild-type females, but histological examination of the ovaries revealed fewer follicles in the homozygous mutants (P ¼ 0.007). Administration of a high-galactose (40% w/w) diet to lactating homozygous GalT gene-trapped females led to lethality in over 70% of the homozygous GalT gene-trapped pups before weaning. Cerebral edema, abnormal changes in the Purkinje and the outer granular cell layers of the cerebellum, as well as lower blood GSH/GSSG ratio were identified in the galactose-intoxicated pups. Finally, reduced growth was observed in GalT gene-trapped pups fed with normal chow and all pups fed with high-galactose (20% w/w) diet. This new mouse model presents several of the complications of Classic Galactosemia and will be useful to investigate pathogenesis and new therapies.

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“…This enzyme catalyses the direct inter-conversion of UDP glucose and UDP galactose (Leloir, 1951), which are precursors involved in the synthesis of capsular polysaccharide and the compatible solute trehalose as well as the synthesis of lipopolysaccharide and membranederived oligosaccharides in Gram-negative bacteria (Fukasawa et al, 1962;Markovitz, 1977;Schulman and Kennedy, 1977;Giaever et al, 1988;Seltman and Holst, 2002;Grundling and Schneewind, 2007). The galE gene is often found in an operon with the galT and galK genes for galactose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Functional metagenomics reveals novel salt tolerance loci from the human gut microbiome

et al. 2012

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Metagenomics is a powerful tool that allows for the culture-independent analysis of complex microbial communities. One of the most complex and dense microbial ecosystems known is that of the human distal colon, with cell densities reaching up to 10 12 per gram of faeces. With the majority of species as yet uncultured, there are an enormous number of novel genes awaiting discovery. In the current study, we conducted a functional screen of a metagenomic library of the human gut microbiota for potential salt-tolerant clones. Using transposon mutagenesis, three genes were identified from a single clone exhibiting high levels of identity to a species from the genus Collinsella (closest relative being Collinsella aerofaciens) (COLAER_01955, COLAER_01957 and COLAER_01981), a high G þ C, Gram-positive member of the Actinobacteria commonly found in the human gut. The encoded proteins exhibit a strong similarity to GalE, MurB and MazG. Furthermore, pyrosequencing and bioinformatic analysis of two additional fosmid clones revealed the presence of an additional galE and mazG gene, with the highest level of genetic identity to Akkermansia muciniphila and Eggerthella sp. YY7918, respectively. Cloning and heterologous expression of the genes in the osmosensitive strain, Escherichia coli MKH13, resulted in increased salt tolerance of the transformed cells. It is hoped that the identification of atypical salt tolerance genes will help to further elucidate novel salt tolerance mechanisms, and will assist our increased understanding how resident bacteria cope with the osmolarity of the gastrointestinal tract.

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The enzymatic transformation of uridine diphosphate glucose into a galactose derivative

Cited by 407 publications

References 6 publications

Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status

Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status

Subfertility and growth restriction in a new galactose-1 phosphate uridylyltransferase (GALT) - deficient mouse model

Functional metagenomics reveals novel salt tolerance loci from the human gut microbiome

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