## 3 Results and Discussion  
### Model Characteristics  
The final version of the iRV781 model includes 781 genes associated with 1221 reactions, among which, 174 are transport reactions, and 196 are external drain reactions (exchange constraints set to mimic the environmental conditions), involving 927 metabolites and four different compartments. Analyzing the distribution of proteins by compartments, 205 are plasma membrane proteins, 521 cytoplasmatic proteins and 139 mitochondrial proteins. In order to elucidate the characteristics of our model we selected well-characterized genome-scale metabolic models of _C. glabata_[41] and _S. cerevisiae_[42] as a comparison. Table 1 shows the distribution of those reactions by the main pathways in the three models. In general, the number of reactions by pathway is quite similar to _C. glabata_, _S. cerevisiae_ or both. Although our model has common standard identifiers for reactions (KEGG ID), it is not possible to assess how the reactions differ among the three models, since the remaining two models do not possess the same identifiers. However, considering only the proteins associated with an EC number, it is possible to make a comparison across the existing models. More than 80% of the proteins with an associated EC number in our model are also present at least in one of the other 2 models (_S. cerevisiae_ or _C. glabata_). Furthermore, about 65% of the proteins are shared by the three models while about 20% are unique in iRV781 (Figure 2). The complete list of unique EC numbers can be found in File S3. In most cases, the observable differences in EC numbers were related to outdated EC numbers or were compensated with other enzymes that are responsible for the same reactions in the model. However, some cases stand out as potential unique features of _C. albicans_:  
* The enzyme 1.13.99.1, inositol oxygenase, responsible for the conversion of myo-inositol into D-glucuronate. This enzyme seems to be involved in resistance to toxic ergosterol analogs [44], \begin{table}
\begin{tabular}{c c c c} \hline  & _C. albicans_ & _C. glabrata_ & _S. cerevisiae_ \\ \hline  & iRV781 & iNX804 & iMM904 \\ \hline Amino acid metabolism & 218 & 223 & 217 \\ NAD biosynthesis & 20 & 20 & 24 \\ Cofactors and vitamins & 122 & 120 & 127 \\ Nucleotide metabolism & 120 & 138 & 135 \\ Alternate carbon & 27 & 31 & 27 \\ metabolism & 26 & 18 & 22 \\ Glycolysis/glucoseogenesis & 24 & 20 & 13 \\ Citrate cycle & 18 & 16 & 13 \\ Pentose phosphate & 31 & 28 & 18 \\ Oxidative & 10 & 13 & 19 \\ Sterol metabolism & 29 & 30 & 49 \\ Fatty acid metabolism & 87 & 81 & 108 \\ Glycerolipid metabolism & 13 & 9 & 12 \\ Phospholipid & 34 & 44 & 52 \\ metabolism & & & \\ \hline \end{tabular}
\end{table} 
Table 1: Number of reactions in the main pathways of the _C. albicans_ iRV781 model in comparison to C. _glabrata_ iNX804 model and _S. cerevisiae_ iMM904 model. Figure 2: Comparison between _C. albicans_, _S. cerevisiae_ and _C. glabrata_ proteins with associated EC Numbers present in the genome-scale metabolic models iRV781, iIN800, and iNX804, respectively. Diagram obtained using VENNY2.1 tool [43]. is also present in other _Candida_ species, including some important pathogens (_C. parapsilosis_, _C. dubliniensis_, _C. auris_), but absent in _C. glabrata_. * The enzyme 1.1.1.289, sorbose reductase, responsible for the interconversion of L-sorbose into D-sorbitol. In fact, the presence this enzyme allows _C. albicans_ to use L-sorbose as carbon source [45], unlike _S. cerevisiae_. * The enzyme 1.14.19.17, sphingolipid 4-desaturase, responsible for the conversion of dihydroceramide into _N_-Acylsphingosine. This protein is involved in sphingolipid metabolism, with possible impact in azide resistance in _C. albicans_[46]. The presence of this enzyme may represent a specific resistance feature of some _Candida_ species, being present in _C. paralysisis_, _C. dubliniensis_, _C. auris_, but not in _C. glabrata_.