Metabolic Network Optimization Simulation

Sustainable production of chemicals is still a major global challenge for humanity in the 21 st century.The current production using biological methods does not fully realize the sustainable development of resources and environment.Therefore,we are prompted to contemplate the artificial intervention of metabolic reactions to regulate,analyze and design pathways guiding experiments to achieve optimal regulation.The main work of this paper focuses on the use of mathematical and computational methods to study metabolic networks.The main achievements are as follows:(1)A metabolic pathway prediction algorithm based on flux balance analysis is proposed.The algorithm can automatically search exogenous reactions insertion host strain model and solve the suboptimal pathway under the conditions that the substance conservation,the reaction rate constraint,the 13C data constraint and the growth rate constraint.The simulation results showed that nine metabolic pathways for the synthesis of 1,3-butanediol were simulated in the E.coli model.The synthetic pathways of adipic acid were simulated in the C.glutamicum model,and eight metabolic pathways were identified.The synthetic pathways of ethylene glycol were simulated in the E.coli model,and four metabolic pathways were identified.(2)Analysis and evaluation of metabolic pathways.The thermodynamic feasibility of the metabolic pathways was analyzed based on the Gibbs free energy and environmental information of the metabolites.Then the effects of growth rate,oxygen,NADH,and NADPH on the carbon conversion rate from substrate to product were analyzed by adjusting the metabolic network model.(3)A new strain optimization algorithm named OptBUCT was proposed.Compared with other strain optimization algorithms,the proposed algorithm can give recommendations for up-regulation,down-regulation and knockout of the reactions,and gives a smaller set of reaction operations.The simulation results showed that in metabolic pathway A for the synthesis of 1,3-butanediol by Escherichia coli,the DERA reaction flux needed to be up-regulated by 97.54%,and the CS reaction flux needed to be down-regulated by 21.87%.In metabolic pathway A for the synthesis of adipic acid by E.coli,the 3OXCOAT reaction flux needed to be up-regulated by 119.08%,the PPC reaction flux needed to be up-regulated by 175.26%,the ACONTa reaction flux needed to be down-regulated by 23.59%,and the SUCDi reaction needed to be knocked out.In metabolic pathway B for the synthesis of ethylene glycol by E.coli,the ETHACL reaction flux needed to be up-regulated by 20.34%,the ACONTa reaction flux needed to be down-regulated by 71.87%,and the SUCDi reaction needed to be knocked out.