## 3 Major Routes of Xylose Transport and Metabolism in Bacteria
### Metabolic Pathways to Xylitol and Xylonic Acid
#### 3.3.2 Xylonic Acid  
Although xylonic acid is a valuable platform chemical that can substitute gluconic acid in a range of applications (from pharmaceuticals to paints, solvents, and adhesives), large-scale production has not yet been developed [124]. In contrast with xylitol, xylonic acid is mainly produced from xylose by bacteria by the unconventional non-phosphorylative pathway (Figure 1). _B. xenovorans_, _C. crescentus_, _G. oxydans_, _P. sacchari_, _P. fagi_, _Pseudoduganella danionis_, and _Pseudomonas putida_ are examples of bacterial native producers, while _Corynebacterium glutamicum_, _E. coli_, and _Klebsiella pneumoniae_ have been engineered to produce xylonic acid [78; 80; 122; 125; 126; 127; 128; 129; 130; 131]. The enzymes that catalyze the conversion of xylose to D-xylonolactone may belong to three different groups based on the cofactor used. Xylose dehydrogenase catalyzes the reaction in _K. pneumoniae_ and is located in the inner membrane of the periplasmic space. It uses pyrroloquinoline quinine (PQQ) as the cofactor [129]. D-xylose dehydrogenase from _Trichoderma resei_ uses NADP\({}^{+}\) as the cofactor, whereas NAD\({}^{+}\) is the cofactor for D-xylose dehydrogenase from _C. crescentus_[78; 132] D-xylose dehydrogenaseases are located in the cytosol. The efficiency of D-xylonolactone production differs greatly depending on the cofactor needed and the location of the dehydrogenase enzymes. D-xylonolactone is then further metabolized into D-xylonate either spontaneously or via xylonolactone, with the activity of this enzyme being induced by the substrate D-xylonolactone [128]. _E. coli_ is an attractive model to produce compounds with biotechnological value, such as xylonic acid, as its physiology and genetics are deeply known and there is a vast amount of genetic and bioinformatic tools available. However, this species does not naturally produce xylonic acid from xylose, as its main metabolic pathway to metabolize xylose is the XI pathway [133; 134]. Nevertheless, this limitation can be circumvented through the use of metabolic engineering. In fact, the heterologous expression of the genes coding for XDH (_xdh_) and xylonolactone (_xyJC_) from _Caubobacter crescentus_ together with the  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Strains** & **C-Source** & **Genetic Modification** & **Growth Conditions** & **Xylitol (g L\({}^{-1}\)) * (g g\({}^{-1}\))** & **Yyjith  
disruption of the genes encoding XI and XK to block xylose utilization via the xylose isomerase pathway as well as of two genes coding for XDY (Figure 1) to prevent further xylonic acid metabolism resulted in xylonic acid accumulation by the genetically modified strain, and up to 27.3 g L\({}^{-1}\) xylonate from 30 g L\({}^{-1}\) xylose was achieved [134; 135]. Besides _E. coli_, _C. glutamicum_ was also modified to enhance xylonic acid production [136]. In this strain, the deletion of the transcriptional repressor gene _iolR_, together with the expression of the xylose uptake IoIT transporter, improved xylose uptake, cell growth, and the sugar conversion into xylonate [137]. The use of recombinant bacteria strains is thus promising and can be a good alternative for xylonic acid production. Bioprocess engineering strategies have also been assessed to attain higher xylonic acid productivities. _G. oxydans_ is a native xylonic acid producer and has been intensively investigated for the production of this metabolite [126; 127; 138; 139; 140]. High volumetric production rates of 4.7 g L\({}^{-1}\) h\({}^{-1}\) with concentrations of 586 g L\({}^{-1}\) have been attained. This species nevertheless has a low biomass production, extremely slow growth, complex nutritional requirements, and thus a high cost in terms of biocatalyst preparation. Moreover, due to the need for high aeration rates, extreme foam production during xylonic acid occurs when air is used for aeration. To circumvent this, pressurized bioreactors and pure oxygen have been used, thus increasing the cost of the production process.