EraGene: A Platform for Harnessing Recurrent Engineering Targets to Guide Metabolite Overproduction in Escherichia coli

EraGene is a platform that compiles experimentally validated engineering targets and production data from engineered Escherichia coli strains for metabolite overproduction. By integrating published metabolic engineering studies, it includes recurrently modified reactions, enabling identification of successful engineering strategies for biochemically related metabolites. We demonstrate its utility through two applications: identifying conserved engineering targets for pathway reinforcement and improving constraint-based metabolic model predictions using experimentally validated modifications. Leave-one-out analysis showed that 75.52% of a metabolite’s engineered reactions were, on average, already annotated for other metabolites, indicating substantial conservation of central metabolism and opportunities for knowledge transfer. Incorporating reactions with conserved modulation direction into QPAML simulations reduced the average search space from 180.21 to 43.51 candidate reactions per metabolite while recovering 81.88% of experimentally validated modifications in the prediction set, corresponding to a 3.41-fold enrichment. At publication, EraGene contained 3,833 production measurements from 2,611 strains across 360 studies, comprising 342 native reactions involving 921 genes. The analytical dataset included 300 native reactions associated with 88 metabolites producible from glucose as the sole carbon source. EraGene is publicly available at https://eragene.com for visualization and data download.