There are at least four different pathways for the catabolism of D-xylose: An oxireductive pathway that is present in eukaryotic microorganisms, an isomerase pathway, and two oxidative pathways that are called Weimberg and Dahms pathway are common in prokaryotic microorganisms.
The oxo-reductive pathway 
This pathway is also called the “Xylose Reductase-Xylitol Dehydrogenase” or XR-XDH pathway. Xylose reductase (XR) and xylitol dehydrogenase (XDH) are the first two enzymes in this pathway. XR is reducing D-xylose to xylitol using NADH or NADPH. Xylitol is then oxidized to D-xylulose by XDH, using the cofactor NAD. In the last step D-xylulose is phosphorylated by an ATP utilising kinase, XK, to result in D-xylulose-5-phosphate which is an intermediate of the pentose phosphate pathway. Because of the varying cofactors needed in this pathway and the degree to which they are available for usage, an imbalance can result in an overproduction of xylitol byproduct.
The isomerase pathway 
Weimberg pathway 
The Weimberg pathway is an oxidative pathway where the D-xylose is oxidized to D-xylono-lactone by a D-xylose dehydrogenase followed by a lactonase to hydrolyze the lactone to D-xylonic acid. A xylonate dehydratase is splitting off a water molecule resulting in 2-keto 3-deoxy-xylonate. A second dehydratase forms the 2-keto glutarate semialdehyde which is subsequently oxidised to 2-ketoglutarate.
Dahms pathway 
Biotechnological applications 
It is desirable to ferment D-xylose to ethanol however microorganisms that are naturally able to do that have disadvantages. One organism that can naturally ferment D-xylose to ethanol is the yeast Pichia stipitis; however it is not as ethanol and inhibitor tolerant as the traditional ethanol producing yeast Saccharomyces cerevisiae. S. cerevisiae on the other hand can not ferment D-xylose to ethanol. In attempts to generate S.cerevisiae strains that are able to ferment D-xylose the XYL1 and XYL2 genes of P. stipitis coding for the XR and XDH respectively were introduced to S. cerevisiae by means of genetic engineering. In another approach a bacterial xylose isomerase was introduced.
Studies on flux through the pentose phosphate pathway during D-xylose metabolism have revealed that limiting the speed of this step may be beneficial to the efficiency of fermentation to ethanol. Modifications to this flux that may improve ethanol production include a) lowering phosphoglucose isomerase activity, b) deleting the GND1 gene, and c) deleting the ZWF1 gene. Since the pentose phosphate pathway produces additional NADPH during metabolism, limiting this step will help to correct the already evident imbalance between NAD(P)H and NAD+ cofactors and reduce xylitol byproduct.
Another experiment comparing the two D-xylose metabolizing pathways revealed that the XI pathway was best able to metabolize D-xylose to produce the greatest ethanol yield, while the XR-XDH pathway reached a much faster rate of ethanol production.
The aim of this genetic recombination in the laboratory is to develop a yeast strain that efficiently produces ethanol. However, the effectiveness of D-xylose metabolizing laboratory strains do not always reflect their metabolism abilities on raw xylose products in nature. Since D-xylose is mostly isolated from agricultural residues such as wood stocks then the genetically altered strains will need to be effective at metabolizing these less pure natural sources.
Varying expression of the XR and XDH enzyme levels have been tested in the laboratory in the attempt to optimize the efficiency of the D-xylose metabolism pathway.
- Weimberg, R. (1961). "Pentose oxidation by Pseudomonas fragi". J. Biol. Chem. 236: 629–636.
- Dahms AS (1974). "3-Deoxy-D-pentulosonic acid aldolase and its role in a new pathway of D-xylose degradation". Biochem Biophys Res Commun 60: 1433–1439. PMID 4423285.
- Eliasson A, Christensson C, Wahlbom CF, Hahn-Hägerdal B (August 2000). "Anaerobic xylose fermentation by recombinant Saccharomyces cerevisiae carrying XYL1, XYL2, and XKS1 in mineral medium chemostat cultures". Appl. Environ. Microbiol. 66 (8): 3381–6. PMC 92159. PMID 10919795.
- Jeppsson et al. (2002). "Reduced Oxidative Pentose Phosphate Pathway Flux in Recombinant Xylose-Utilizing Saccharomyces cerevisiae Strains Improves the Ethanol Yield from Xylose". Applied and Environmental Microbiology. doi:10.1128/AEM.68.4.1604-1609.2002.
- Karhumaa et al. (2007). "Comparison of the xylose reductase-xylitol dehydrogenase and the xylose isomerase pathways for xylose fermentation by recombinant Saccharomyces cerevisiae". Microbial Cell Factories. doi:10.1186/1475-2859-6-5.