Genome-Scale Reconstruction And Analysis Of The Metabolic Network In Bacillus Licheniformis WX-02

Bacillus licheniformis is an industrial production strain having various applications for different aspects. Especially, Poly-y-glutamic acid (γ-PGA) plays an important role in food, medical and environment protection. Genome-scale metabolic network integrates several kinds of data, so we can analyzemetabolic characteristics and pathway of B. licheniformis in a system level. We built a genome-scale metabolic network model iZH1008based on Bacillus subtilis metabolic model iBsu11O3and integrated KAAS annotation, phenotype microarray data and large amounts of literature-derived information. iZH1008encompassed1761metabolic reactions and1105metabolites. We then made a COG function classification for1008genes in this model, and found iZH1008contains a majority of metabolic reactions necessary for growth. Subsequently, the model was validated using the OmniLog Phenotype MicroArray technology and the overall agreement was approximately81%using iZH1008. Furthermore, we screened for necessary genes using iZH1008in M9and LB cultural conditions, deriving235and195necessary genes respectively. Classification of these necessary genes indicates that they are mainly involved in macromolecular synthesis. Because of the lack of data on experimentally necessary gene in B.licheniformis, we compared the necessary genes derived from simulation with those based on the experiment on B.subtilis in LB cultural conditions. The result shows B.licheniformis and B.subtilis share149necessary genes and B.licheniformis has49unique necessary genes. The49unique necessary genes provide a theoretical foundation for validation in the future. At last, we analyzed the topological structure of the metabolic network, found several key nodes in y-PGA synthesis and optimized a pathway of γ-PGAproduction in B.licheniformisWX-02. This will provide aguidance for large-scale industrial production.