## 3 Major Routes of Xylose Transport and Metabolism in Bacteria
### Xylose Metabolic Network in Bacteria
The pyruvate undergoes an oxidative decarboxylation to form acetyl-coenzyme A (acetyl-CoA), which is further oxidized via the Krebs cycle (KC) to generate energy. In the non-phosphorylative pathway, xylose can be converted either to \(\alpha\)-ketoglutate (Weimberg route) or to pyruvate and glucoaldehyde (Dahms route) via a 2-keto-3-deoxy-xylonate intermediate. _Burkholderia xenovorans_, _Caulobacter crescentus_, _Gluconobacter oxydans_, _Paraburkholderia sacchari_, _Pseudomonas fragi_, and _Pseudomonas taitwanensis_ are examples of native bacteria that use this pathway to metabolize xylose, with xylose being converted into D-xylonolactone via XDH (Figure 1) [89; 90; 91]. D-xylonolactone is in turn converted to D-xylonate, which is further converted to 2-keto-3-deoxy-xylonate, the common intermediate to both routes. In the Weimberg pathway (first discovered in _P. fragi_), 2-keto-3-deoxy-xylonate can be metabolized to \(\alpha\)-ketoglutate semialdehyde and then to \(\alpha\)-ketoglutate, a KC intermediate [90]. Alternatively, in the Dahms route, 2-keto-3-deoxy-xylonate can be cleaved to pyruvate and glucoaldehyde [92]. While pyruvate is then directly converted to acetyl-CoA and enters the central carbon metabolism (CCM), glucoaldehyde is incorporated into CCM at the level of glyoxylate, which requires two reactions generating two reduced equivalents. This has been observed in the hyperthermophilic archaea _Sulflobbus solfataricus_[93]. In shake flask assays with recombinant _Saccharomyces cerevisiae_, [PERSON] et al. (2019) observed a low consumption of D-xylose because of the acidification caused by the excretion of D-xylonate to the medium. Furthermore, a deficient NAD\({}^{+}\) recycling mechanism caused by a low oxygen titer was pointed out as the reason for the low efficiency of the oxidative Weinberg pathway. In bioreactor experiments, the accumulation of \(\alpha\)-ketoglutate semialdehyde was detected. This together with the accumulation of D-xylonate suggest the activity of KSH and XDH as rate-controlling steps caused by a deficient regeneration of the needed coenzymes NAD\({}^{+}\) and NADP\({}^{+}\)[94]. These results are in line with the observations of [PERSON] et al. 2020, who, based on a quantitative model for the Weimberg pathway, have proposed these two reactions to be sensitive steps. Those authors, based on metabolic control analyses, found the dehydrogenases to control at high NADH levels while the dehydratase KDY controls at lower NADH levels [95]. Enzyme activity assays in _Caulobacter crescentus_ showed that the Weimberg route is active in bacterial cells grown on xylose but not in the presence of glucose, indicating that the CCR mechanism is also present in this pathway [96]. The non-phosphorylorylative pathway has several advantages compared with the isomerase and oxidoreductase pathways because it directly converts D-xylose towards pyruvate and \(\alpha\)-ketoglutarate (a KC cycle intermediate) by-passing the PPP, thus minimizing the number of enzymatic steps and the usage of ATP. In addition to saving P, the Weimberg pathway also conserves carbon during xylose metabolism and is thus a very efficient route. The positive aspects of the oxidative pathway promoted the development of recombinant strains using this pathway for the production of different valuable compounds as reviewed by [PERSON] et al. [97]. Target products such as 1,2,4-butanetriol, butanetiol, glutaratic acid, \(\gamma\)-aminobutyric acid, and 3,4-dihydroxybutyrate acid have been produced from the Weimberg pathway, while glycolic acid, ethylene glycol, and acetoin were obtained using the Dahms pathway. Particularly for glycolic acid or ethylene glycol, there are no known natural microbial pathways to directly produce these metabolites from carbohydrates. For this reason, attempts to attain high product yields and productivities are still being assessed by several authors through the establishment of synthetic pathways from pentoses, hexoses, or ethanol and using industrial microorganisms such as _E. coli_, _C.