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Levan is a fructan polymer with many industrial applications such as the formulation of hydrogels, drug delivery, and wound healing, among others. To this end, metabolic systems engineering is a valuable method to improve the yield of a specific metabolite in a wide range of bacterial and eukaryotic organisms. In this study, we report a systems biology approach integrating genomics data for the Bacillus subtilis model, wherein the metabolic pathway for levan biosynthesis is unpacked. We analyzed a revised genome-scale enzyme-constrained metabolic model (ecGEM) and performed simulations to increase levan biopolymer production capacity in B. subtilis. We used the model ec_iYO844_lvn to (1) identify the essential genes and bottlenecks in levan production, and (2) specifically design an engineered B. subtilis strain capable of producing higher levan yields. The FBA and FVA analysis showed the maximal …