HESD: A Database of Candidate Reactions and Enzymes for Metabolic Engineering of Corynebacterium glutamicum

The effect of a heterologous enzyme depends on the position of its reaction within the host metabolic network. We present HESD, a database of candidate reactions for heterologous introduction into Corynebacterium glutamicum ATCC 13032 with assessments of network position and feasibility. Rhea release 141, ChEBI and UniProtKB/Swiss-Prot data were integrated with the genome-scale model iCGB21FR, linking reaction variants to 32,619 protein records, with taxonomic assignments for 32,577 records from 3149 taxa. HESD contains 846 variants with both main substrate–product pair metabolites represented in the model and 3642 with one represented metabolite. Variants were classified topologically and assessed for stoichiometric balance, flux feasibility and energy-generating cycles. After excluding variants forming energy-generating cycles, 406 of 525 fully mapped variants retained feasible flux under loopless flux balance analysis. Topological classification agreed for 87.5% of variants shared with the independent model iCW773. Reaction RHEA:79573, catalyzed by ArcE from Thermococcus kodakarensis, replaced two consecutive steps catalyzed by ArgG and ArgH and increased predicted maximum L-arginine flux by 22.7% in iCGB21FR supplemented with Ddh and 12.5% in iCW773 with native Ddh, at a minimum growth rate of 0.05 h−1. HESD supports candidate selection for modeling and experimental validation.