Macrodynamics and cell metabolic flux coupling modeling method in lysine biological manufacturing

Abstract

The invention provides a macrodynamics and cell metabolic flux coupling modeling method in lysine biological manufacturing, belongs to the field of industrial microorganism manufacturing process modeling technologies and application, and relates to a modeling method combining fermentation dynamics expressed by a differential equation with cell metabolic flux described by chemometrics. Through reduction of a complex lysine metabolic network, correlation between key metabolic flux and external measurable variables is established, and coupling of a metabolic flux balance equation and concentration change kinetics of glucose, lysine and biomass is achieved; a coupling model parameter identification method utilizing an intelligent random optimization algorithm is provided, so that not only canthe change of extracellular macroscopic variable concentration be described, but also the dynamic change of intracellular metabolic flux can be described; compared with a common kinetic model, the model precision is high, and means are provided for exploring micromechanism information and metabolic characteristics in microbial cells.

Description

technical field [0001] The invention belongs to the field of modeling technology and application of industrial microbial manufacturing process, and relates to a modeling method that combines fermentation kinetics expressed by differential equations with cell metabolic flux described by chemometrics. The coupling model constructed based on this method can be used It is used in the prediction of biomass concentration, product concentration and substrate concentration during the biomanufacturing process of lysine, and it is also used to reflect and predict the change rule of intracellular metabolic flow. Background technique [0002] Lysine is one of the essential amino acids for the human body. It can promote the growth and development of the body. It is an important nutrient. It has a wide demand in food, medicine, feed and other industries. my country has gradually become the largest producer of lysine in the world. Studying the biomanufacturing process of lysine and using te...

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Problems solved by technology

Analyzing the above kinetic modeling method, directly using the empirical data in the literature, the model is simple but difficult to adapt to the specific production process; and using the experimental data for parameter identification, although there are many identification algorithms to choose from, but the single ones about biomass, product The structure of the differential equation for the change of substrate concentration and substrate concentration fundamentally limits the accuracy and application range of this type of kinetic model

Considering that the most widespread species in industrial lysine production is Corynebacterium glutamicum, the central metabolic network of Corynebacterium glutamicum was given in some literatures by carbon flux model and NMR spectroscopy, and the complete lysine The metabolic network of amino acid fermentation has been improved, but the complete genome-scale metabolic network is very complex, including a large number of reactions and metabolites, and it is very difficult to directly use it for modeling and application

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