## 3 Major Routes of Xylose Transport and Metabolism in Bacteria
### Xylose Metabolic Network in Bacteria  
Xylose can be naturally metabolized by several microorganisms, including bacteria belonging to Archaea domain, Clostridia, proteobacteria, yeast, and filamentous fungi [70; 71]. In order to optimize pentose utilization, genetic manipulation based on metabolic engineering has also been used to obtain yeast and bacterial recombinant strains with improved capacity to transport and metabolize xylose [72; 73; 74]. Xylose is consumed mainly through three different metabolic pathways: (i) the isomerase pathway; (ii) the oxidoreductase pathway; and (iii) the oxidative pathway, also recognized as the non-phosphorylative pathway. The xylose metabolic network scheme is represented in Figure 1. The isomerase pathway converts xylose into xylulose, which is then phosphorylated to xylulose phosphate entering the pentose phosphate pathway (PPP). This is typically used by prokaryotes, namely by _E.coli_, _Bacillus_ sp., and _Lactobacillus_ sp. [75; 76; 77; 78]; the oxidoreductase pathway is mostly present in eukaryotic microorganisms. Here, xylose is first converted to xylitol, which is then dehydrogenated and phosphorylated to xylulose phosphate, entering the PPP. The oxidative pathway has a common trunk that divides in two branches: the Weinberg and the Dahms pathways. This oxidative pathway is mainly carried out by bacteria. Figure 1: Three pathways of xylose metabolization by microorganisms: solid light blue, Weinberg pathway; dashed dark blue, Dahms pathway; dashed green, oxidoreductase pathway; and solid red, isomerase pathway. The enzymes are abbreviated as follows: acetyl-CoA synthase (ACS); acetate kinase (AK); enolase (EL); glyceraldehyde-3-phosphate dehydrogenase (GPDH); 2-keto-3-deoxyxylonate dehydratase (KDY); \(\alpha\)-ketoglutarate semaldehyde dehydrogenase (KSH); pyrophosphate-acetate phosphotransferase (PAP); pyruvate dehydrogenase complex (PDC); 3-phosphoglycerate kinase (PGK); phosphoketolase (PK); phosphoketolase (PKL); xylonate dehydratase (XDY); xylose dehydrogenase (XDH); xylitol dehydrogenase (XOHDH); xylose isomerase (XI); xylulokinase (XK); xylololactonese (XLS); and xylose reductase (XR). Adapted from [79; 80]. Regarding the isomerase pathway, xylose is first isomerized to xylulose by the enzyme xylose isomerase (Figure 1). Xylulose is then phosphorylated to xylulose-5-phosphate by XK (Figure 1). Genes coding for both enzymes are induced by xylose and repressed by glucose and other more readily usable substrates, according to the CCR mechanism, previously reported [62; 81]. Xylose isomerase may be activated in the presence of divalent ions such as Mg\({}^{2+}\), Co \({}^{2+}\), or Mn \({}^{2+}\), whereas others such as Ca \({}^{2+}\) act as inhibitors [41]. This enzyme may also be strongly inhibited by polyol xylitol, especially at a pH below 6 [82; 83]. The metabolism of xylulose-5-phosphate continues generally via the PPP pathway, entering the central carbon metabolism. The PPP consists of several reversible transketolase and transaldolase reactions, of which the main function is to produce NAD(P)H, thus providing the reducing power for biosynthetic reactions [84]. Some bacteria, however (e.g., _Clostridium acetobutylcium_, _Clostridium beijerinclii_, and _Lactococcus lactis_), present an alternative mechanism, cleaving xylulose-5-P into acetylcholinesterase phosphate and glyceraldehyde-3-phosphate in a reaction catalyzed by phosphoketolase [85; 86; 87]. The oxidoreductase pathway is more common in yeast and fungi and uses two steps for the conversion of xylose in xylulose, employing the enzymes XR and XDH (Figure 1), with xylitol being an intermediate in this conversion [88]. Xylulose is then further metabolized via XK and PPP (Figure 1). Either via the isomerase or the oxidoreductase pathways, carbon exits the sugar-phosphate pool by various routes, with one of them being responsible for the formation of pyruvate.