## 3 Major Routes of Xylose Transport and Metabolism in Bacteria
### Mechanisms of Xylose Transport  
The transport of nutrients to the cells is the first step in their metabolic utilization. In order to transport sugars and other nutrients in and out of the cells, various organisms can use different types of transport mechanisms. Regarding D-xylose, yeast and fungi can use facilitated diffusion or active transport, while bacteria tend to use active transport mechanisms [41]. These types of mechanisms are mediated by carrier proteins and, hence, exhibit the properties of specific inhibition, substrate specificity, and saturability. These processes enable sugar transportation against a concentration gradient at the expense of metabolic energy. Bacteria species such as _Bacillus_, _Clostridium_, _Escherichia coli_, and _Lactococcus_ use active transport for the uptake of xylose into the cell [41; 44]. Usually, there are high- and low-affinity transporter routes. In _E. coli_, the most studied species, the high-affinity transporter (XyIFGH) belongs to the ATP-binding cassette (ABC) family, while the low-affinity transporter (XlyE), a proton-coupled symporter, belongs to the major facilitator superfamily (MFS), with xylose transport being driven by a proton motive force [45; 46; 47; 48]. The low-affinity transport mechanism is also present in _Bacillus megaterium_, _Bacillus subtilis_, _Lactobacillus brevis_, _Salmonella typhimurium_, _Tetragencococcus halophila_, and some ruminal bacteria [49; 50; 51; 52; 53; 54; 55]. The ABC transporter is more efficient concerning xylose uptake and comprises a D-xylose-binding protein XylF, the membrane permease XylH, and the ATP-binding protein XylG [48; 56]. This system is also present in bacteria such as _Clostridium_, _Geobacillus_, or _Theromanerobacter species_[41; 57; 58; 59]. However, this transport can be inhibited when other readily fermentable substrates, such as glucose, are present. Many microbial strains have a regulatory mechanism, carbon catabolite repression (CCR), mainly mediated by components of the phosphoenolpyruvate (PEP): carbohydrate phosphotransferase system (PTS), which prevents the expression of genes needed for catabolism of other carbon sources, namely pentoses, while the substrate that enables the fastest growth (normally glucose) is present [60; 61]. Concerning _E. coli_, at least two mechanisms of xylose transport and metabolism repression were reported, including the XylR regulator and cyclic AMP (cAMP) receptor protein (CRP)-dependent control of Xyl genes and the presence of arabin, since the transporters allow for the transportation of this sugar at lower efficiencies [62]. The presence of high levels of glucose leads to the dephosphorylation of the component EIIA of PTS, which becomes unable to activate the enzyme adenylate cyclase, originating low levels of cAMP. In contrast, when glucose levels drop, cAMP increases, activating CRP that, together with XylR (activated when bound by xylose), stimulate the operons xylRFGH and xylAB, involved in xylose transport and metabolism [53]. These repressive mechanisms could bring difficulties in the utilization of lignocellulosic hydrolysates, where both sugars are present. In this kind of media, a diauxic growth is observed and the preferential substrate, usually glucose, is consumed first. When glucose is depleted in the culture medium and another non-repressive substrate such as xylose is present, there is a temporary cessation of growth and catabolic repression is then relieved. As previously said, these repression mechanisms are found in _E. coli_, where several exponential phases separated by lag phases can be observed when a sugar mix is supplied as a carbon source to the cultivation, indicating a sequential sugar consumption [63]. A repression behavior is also present in other bacteria strains. In _P. sacchari_, when the cells are grown in a medium containing glucose, xylose, and citric acid, the uptake of glucose and xylose only takes place when the citric acid has been completely consumed. _P.