title: Metabolic model reconstruction and analysis of an artificial microbial ecosystem for vitamin C production.
abstract: An artificial microbial ecosystem (AME) consisting of Ketogulonicigenium vulgare and Bacillus megaterium is currently used in a two-step fermentation process for vitamin C production. In order to obtain a comprehensive understanding of the metabolic interactions between the two bacteria, a two-species stoichiometric metabolic model (iWZ-KV-663-BM-1055) consisting of 1718 genes, 1573 metabolites, and 1891 reactions (excluding exchange reactions) was constructed based on separate genome-scale metabolic models (GSMMs) of K. vulgare and B. megaterium. These two compartments (k and b) of iWZ-KV-663-BM-1055 shared 453 reactions and 548 metabolites. Compartment b was richer in subsystems than compartment k. In minimal media with glucose (MG), metabolite exchange between compartments was assessed by constraint-based analysis. Compartment b secreted essential amino acids, nucleic acids, vitamins and cofactors important for K. vulgare growth and biosynthesis of 2-keto-l-gulonic acid (2-KLG). Further research showed that when co-cultured with B. megaterium in l-sorbose-CSLP medium, the growth rate of K. vulgare and 2-KLG production were increased by 111.9% and 29.42%, respectively, under the constraints employed. Our study demonstrated that GSMMs and constraint-based methods can be used to decode the physiological features and inter-species interactions of AMEs used in industrial biotechnology, which will be of benefit for improving regulation and refinement in future industrial processes.
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China. Electronic address: mingll@jiangnan.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
mesh_terms: D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism*; D001410:Bacillus megaterium / Q000378:metabolism*; D007218:Industrial Microbiology / Q000379:methods*; D060847:Metabolic Engineering / Q000379:methods*; D059013:Microbial Consortia; D008954:Models, Biological; D041902:Rhodobacteraceae / Q000378:metabolism*
chemical_list: D001205:Ascorbic Acid
keywords: Artificial microbial ecosystem; Bacillus megaterium; Genome-scale metabolic models; Ketogulonicigenium vulgare; Vitamin C