New Insights on Metabolic Features of Bacillus subtilis Based on Multistrain Genome-Scale Metabolic Modeling

Bacillus subtilis is an effective workhorse for the production of many industrial products. The high interest aroused by B. subtilis has guided a large metabolic modeling effort of this species. Genome-scale metabolic models (GEMs) are powerful tools for predicting the metabolic capabilities of a given organism. However, high-quality GEMs are required in order to provide accurate predictions. In this work, we construct a high-quality, mostly manually curated genome-scale model for B. subtilis (iBB1018). The model was validated by means of growth performance and carbon flux distribution and provided significantly more accurate predictions than previous models. iBB1018 was able to predict carbon source utilization with great accuracy while identifying up to 28 metabolites as potential novel carbon sources. The constructed model was further used as a tool for the construction of the panphenome of B. subtilis as a species, by means of multistrain genome-scale reconstruction. The panphenome space was defined in the context of 183 GEMs representative of 183 B. subtilis strains and the array of carbon sources sustaining growth. Our analysis highlights the large metabolic versatility of the species and the important role of the accessory metabolism as a driver of the panphenome, at a species level.