This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Carbohydrates Degradation → Sugars Degradation → Galactose Degradation|
Expected Taxonomic Range: Fungi
The fungi Trichoderma reesei (previously known as Hypocrea jecorina), Aspergillus niger and Aspergillus nidulans have been shown to catabolize β-D-galactose by two pathways, the Leloir pathway (see pathway galactose degradation I (Leloir pathway)) and a second pathway that involves a series of reductive and oxidative steps. In the oxidoreductive pathway, β-D-galactose is converted to β-D-fructofuranose by multiple NADPH-dependent reduction reactions and NAD+-dependent oxidation reactions via the intermediates galactitol, L-xylo-3-hexulose, and D-sorbitol. A previously missing enzyme in the pathway, L-xylo-3-hexulose reductase, was identified which provides the activity that catalyzes the conversion of L-xylo-3-hexulose to D-sorbitol [Mojzita12].
The first three reactions of this second pathway have been experimentally established in Aspergillus niger and Trichoderma reesei, and the intermediate L-xylo-3-hexulose has been identified in vitro using recombinant lad1 from Trichoderma reesei and recombinant ladB from Aspergillus niger ATCC 1015 [Mojzita12a, Mojzita12]. However in Aspergillus nidulans mutant analysis suggested that L-sorbopyranose is a pathway intermediate and its catabolism involves a hexokinase step. The catabolism of β-D-galactose also represents part of the catabolism of the galactose-containing disaccharide α-lactose, as well as galactose-containing, plant-derived hemicellulose and pectin (reviewed in [Kubicek09, Seiboth11]).
In Aspergillus niger, β-D-galactose reduction to galactitol is catalyzed by D-xylose reductase (aldose reductase) encoded by xyrA. However, unlike Trichoderma reesei and Aspergillus nidulans in which Lad1 is used in the oxidation of both galactitol and L-arabitol, in Aspergillus niger LadB functions as a specific galactitol-3-dehydrogenase that is not involved in pentose metabolism. LadA functions as an L-arabitol dehydrogenase in this organism [Mojzita12a, Koivistoinen12]. The gene encoding sorbitol dehydrogenase sdhA in Aspergillus niger has also been identified, cloned and its product characterized [Koivistoinen12].
About This Pathway
Trichoderma reesei can catabolize β-D-galactose by both the Leloir pathway (see pathway galactose degradation I (Leloir pathway)) and this second, reductive pathway in which β-D-galactose is reduced to galactitol by an aldose reductase encoded by gene xyl1. This enzyme is also operative in the initial reduction step in the L-arabinose and α-D-xylopyranose catabolic pathways in this organism (see pathways L-arabinose degradation II and xylose degradation II). In the second step galactitol has been shown in vitro to be oxidized to L-xylo-3-hexulose by the product of gene lad1, which also oxidizes L-arabitol (see pathway L-arabinose degradation II) [Pail04, Seiboth07, Seiboth04].
In Trichoderma reesei the third step is catalyzed by L-xylo-3-hexulose reductase encoded by gene lxr4 and in Aspergillus niger by gene xhrA. Deletion mutants lacking these genes did not grow on galactitol and showed reduced growth on β-D-galactose. The product of gene lxr4 was shown to specifically catalyze the conversion of L-xylo-3-hexulose to D-sorbitol [Mojzita12]. In the fourth step the product of Trichoderma reesei gene xdh1 has been shown to utilize D-sorbitol as well as xylitol [Seiboth03].
In Aspergillus nidulans there is also evidence for this second pathway, but differences from Trichoderma reesei might exist. In Aspergillus nidulans mutant analysis suggested that L-sorbopyranose was an intermediate of this pathway [Fekete04]. The catabolism of L-sorbopyranose is known to occur by reduction to D-sorbitol, oxidation of D-sorbitol to D-fructose, and phosphorylation of D-fructose to β-D-fructofuranose 6-phosphate which enters glycolysis (reviewed in [Seiboth11]).
The physiological importance of this pathway may also differ between fungi. In Aspergillus nidulans the pathway can fully compensate for loss of the Leloir pathway, but in Trichoderma reesei it cannot and inactivation of the Leloir pathway results in impairment of growth on β-D-galactose (reviewed in [Kubicek09, Seiboth11]).
Fekete04: Fekete E, Karaffa L, Sandor E, Banyai I, Seiboth B, Gyemant G, Sepsi A, Szentirmai A, Kubicek CP (2004). "The alternative D-galactose degrading pathway of Aspergillus nidulans proceeds via L-sorbose." Arch Microbiol 181(1);35-44. PMID: 14624333
Koivistoinen12: Koivistoinen OM, Richard P, Penttila M, Ruohonen L, Mojzita D (2012). "Sorbitol dehydrogenase of Aspergillus niger, SdhA, is part of the oxido-reductive d-galactose pathway and essential for d-sorbitol catabolism." FEBS Lett 586(4);378-83. PMID: 22245674
Kubicek09: Kubicek CP, Mikus M, Schuster A, Schmoll M, Seiboth B (2009). "Metabolic engineering strategies for the improvement of cellulase production by Hypocrea jecorina." Biotechnol Biofuels 2;19. PMID: 19723296
Mojzita12: Mojzita D, Herold S, Metz B, Seiboth B, Richard P (2012). "L-xylo-3-hexulose reductase is the missing link in the oxidoreductive pathway for D-galactose catabolism in filamentous fungi." J Biol Chem 287(31);26010-8. PMID: 22654107
Mojzita12a: Mojzita D, Koivistoinen OM, Maaheimo H, Penttila M, Ruohonen L, Richard P (2012). "Identification of the galactitol dehydrogenase, LadB, that is part of the oxido-reductive d-galactose catabolic pathway in Aspergillus niger." Fungal Genet Biol 49(2);152-9. PMID: 22155165
Pail04: Pail M, Peterbauer T, Seiboth B, Hametner C, Druzhinina I, Kubicek CP (2004). "The metabolic role and evolution of L-arabinitol 4-dehydrogenase of Hypocrea jecorina." Eur J Biochem 271(10);1864-72. PMID: 15128296
Seiboth03: Seiboth B, Hartl L, Pail M, Kubicek CP (2003). "D-xylose metabolism in Hypocrea jecorina: loss of the xylitol dehydrogenase step can be partially compensated for by lad1-encoded L-arabinitol-4-dehydrogenase." Eukaryot Cell 2(5);867-75. PMID: 14555469
Seiboth04: Seiboth B, Hartl L, Pail M, Fekete E, Karaffa L, Kubicek CP (2004). "The galactokinase of Hypocrea jecorina is essential for cellulase induction by lactose but dispensable for growth on d-galactose." Mol Microbiol 51(4);1015-25. PMID: 14763977
Seiboth07: Seiboth B, Gamauf C, Pail M, Hartl L, Kubicek CP (2007). "The D-xylose reductase of Hypocrea jecorina is the major aldose reductase in pentose and D-galactose catabolism and necessary for beta-galactosidase and cellulase induction by lactose." Mol Microbiol 66(4);890-900. PMID: 17924946
Aguayo13: Aguayo MF, Ampuero D, Mandujano P, Parada R, Munoz R, Gallart M, Altabella T, Cabrera R, Stange C, Handford M (2013). "Sorbitol dehydrogenase is a cytosolic protein required for sorbitol metabolism in Arabidopsis thaliana." Plant Sci 205-206;63-75. PMID: 23498864
Akel09: Akel E, Metz B, Seiboth B, Kubicek CP (2009). "Molecular regulation of arabinan and L-arabinose metabolism in Hypocrea jecorina (Trichoderma reesei)." Eukaryot Cell 8(12);1837-44. PMID: 19801419
Caescu04: Caescu CI, Vidal O, Krzewinski F, Artenie V, Bouquelet S (2004). "Bifidobacterium longum requires a fructokinase (Frk; ATP:D-fructose 6-phosphotransferase, EC 18.104.22.168) for fructose catabolism." J Bacteriol 186(19);6515-25. PMID: 15375133
Chi09: Chi A, Rhee S (2009). "The functional annotation of Arabidopsis protein sequences was performed by BLAST queries against a reference set of experimentally verified enzymes. For each Arabidopsis sequence, the enzymatic activity of the top BLAST hit (or hits if they had equivalent E-values) was assigned to the protein if its E-value fell below a specific E-value threshold established for the corresponding enzymatic activity. Note: The annotation thresholds were established by doing a self BLAST of the reference enzyme dataset. For each enzymatic activity represented by multiple proteins, the mean E-value of all the correct hits generated by the self BLAST was selected as the cut-off. All of these means were averaged and used as the cut-off for assigning annotations for any enzymatic activities that were represented by a single protein in the reference dataset."
Dai99: Dai N, Schaffer A, Petreikov M, Shahak Y, Giller Y, Ratner K, Levine A, Granot D (1999). "Overexpression of Arabidopsis hexokinase in tomato plants inhibits growth, reduces photosynthesis, and induces rapid senescence." Plant Cell 11(7);1253-66. PMID: 10402427
Giese05: Giese JO, Herbers K, Hoffmann M, Klosgen RB, Sonnewald U (2005). "Isolation and functional characterization of a novel plastidic hexokinase from Nicotiana tabacum." FEBS Lett 579(3);827-31. PMID: 15670855
Helanto06: Helanto M, Aarnikunnas J, Palva A, Leisola M, Nyyssola A (2006). "Characterization of genes involved in fructose utilization by Lactobacillus fermentum." Arch Microbiol 186(1);51-9. PMID: 16741753
Kornberg00: Kornberg HL, Lambourne LT, Sproul AA (2000). "Facilitated diffusion of fructose via the phosphoenolpyruvate/glucose phosphotransferase system of Escherichia coli." Proc Natl Acad Sci U S A 97(4);1808-12. PMID: 10677538
MartinezBarajas97: Martinez-Barajas E, Krohn BM, Stark DM, Randall DD (1997). "Purification and characterization of recombinant tomato fruit (Lycopersicon esculentum Mill.) fructokinase expressed in Escherichia coli." Protein Expr Purif 11(1);41-6. PMID: 9325137
Oura00: Oura Y, Yamada K, Shiratake K, Yamaki S (2000). "Purification and characterization of a NAD+-dependent sorbitol dehydrogenase from Japanese pear fruit." Phytochemistry 54(6);567-72. PMID: 10963448
Simpson09: Simpson PJ, Tantitadapitak C, Reed AM, Mather OC, Bunce CM, White SA, Ride JP (2009). "Characterization of two novel aldo-keto reductases from Arabidopsis: expression patterns, broad substrate specificity, and an open active-site structure suggest a role in toxicant metabolism following stress." J Mol Biol 392(2);465-80. PMID: 19616008
Sprenger88: Sprenger GA, Lengeler JW (1988). "Analysis of sucrose catabolism in Klebsiella pneumoniae and in Scr+ derivatives of Escherichia coli K12." J Gen Microbiol 1988;134 ( Pt 6);1635-44. PMID: 3065452
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