Figure 1 iML1515 genome-scale reconstruction.(a) The iML1515 model contains 1,515 open reading frames that encode enzymes that catalyze 2,719 reactions involving 1,192 unique metabolites. It also includes 1,515 protein structures. All reconstruction content is linked to external databases, including KEGG, PDB, and CHEBI. iML1515 is capable of performing flux-balance analysis to integrate and interpret a variety of emerging data types including linking mutations identified from resequencing and/or transcriptomics data to fluxomics.(b) All reactions are linked to encoding gene (s) and protein. Connection to PDB structures and homology models form a domain-gene-protein-reaction relationship (dGPR)(Supplementary Data set 7).(c) Clustering of domain architecture and metabolite usage provides tools to explore enzyme promiscuity and metabolism25, 28. The domain-connectivity network can be visualized using Cytoscape and is supplied as a network file (Supplementary Data set 8). The acetyltransferase domain in c highlights a specific example of domain connectivity. The acyltransferase domain (d1iuqa_) is present in three genes (b3018, b1054, and b2378). The encoded proteins catalyze different but related reactions in glycerophospholipid metabolism and endotoxin synthesis. All reactions are ACP-dependent acyltransferases.(d) A database consisting of 333 normalized transcriptomics data sets15 was contextualized using the GPRs of iML1515. Relative expression for all three genes catalyzing the ASPK reaction are plotted across all experimental conditions, revealing condition-specific preferences for gene usage. The experimental conditions that favor a particular isozyme are listed. At the top of the panel two reactions (ASPK, HSDy) are shown with two isozymes that can catalyze these reactions (ThrA, MetL). The third isozyme (LysC) can only catalyze APSK. ASPK and HSDy activity must be present to synthesize L-threonine (thr-L), L-methionine (met-L), L-isoleucine (ile-L), biotin (btn), and S-adenosyl-L-methionine (amet). Only ASPK activity is needed to synthesize murein derivatives and L-lysine (lys-L)(further discussion can be found in Supplementary Fig. 8 and Supplementary Note 6). a c d b