A microbial fermentation process amplification platform technology

Abstract

The invention provides a microorganism fermentation process scaling-up platform technique. In the process of fermentation, symbolic metabolites are chosen to reflect the growing state of microorganisms and the condition of fermentation medium, and by controlling the change of the symbolic metabolites, and combined with hydromechanics to calculate, design and improve the size and structure of a stirring reactor, the gas holdup is increased and the concentration of the symbolic metabolites is decreased; and fermentation conditions are optimized and the fermentation process is scaled up. The technique is applied in the production of glutathione and S-adenosine-L-methionine and the coproduction of glutathione and ergosterol by brewing yeast fermentation and the production of hyaluronic acid by streptococcus zooepidemicus fermentation. The symbolic metabolites are ethanol, glycerin, lactic acid and acetic acid. The technique ensures that the concentration of ethanol in the high-density aerobic fermentation of yeast is less than 0.5 percent and that the concentration of lactic acid as the symbolic metabolite in the production of hyaluronic acid by bacterial fermentation is less than 3 percent. The technique is easy to operate, and the automation degree is high; and the application range is wide, and the technique can be used in the yeast system as well as the bacteria system.

Description

[0001] Technical field: [0002] The invention relates to a microbial fermentation process amplification platform technology. In the fermentation process, marker metabolites are selected to reflect the growth status of microorganisms and the condition of fermentation medium, and the improvement is designed by controlling the changes of marker metabolites and combining fluid mechanics calculations. Stir the size and structure of the reactor, increase the gas holdup, optimize the fermentation conditions, and scale up the fermentation process. [0003] Background technique: [0004] In the process of high-density fermentation, because many nutrients have inhibitory effect on cells at high concentrations, in order to solve the inhibition of high-concentration substrates, fed-batch fermentation has been widely used in high-concentration fermentation of various microorganisms. For example, in Japan's research in 1992, the fermentation strain was Saccharomyces cerevisiae KY6186 re...

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Problems solved by technology

Power per unit volume, mixing time and other parameter value similarity criterion; quasi-number rule amplification (industrial amplification), equal amplification according to oxygen transfer coefficient, linear velocity, etc.; N-S equation-based computational fluid dynamics amplification and multi-scale parameter sum proposed by Professor Nello in the UK Computational fluid dynamics amplification (East China University of Science and Technology), that is, to amplify the correlation between the macroscopic physical parameters of the fermentation process and the parameters of biological physiological characteristics such as RQ, OUR, and CER. The parameters include temperature, dissolved oxygen, pH, and CO in the fermentation tail gas. 2 and O 2 The concentration change of the fermentation process is used to guide the scale-up of the fermentation process, but only the influence of the reactor on the fermentation process is considered, and the molecular level metabolic changes in the microbial fermentation process are not considered, and the scale-up still partly depends on experience

[0006] To sum up, the exponential / constant-rate feeding method or the method of controlling a certain concentration of substrate feeding involved in microbial fermentation production, as well as the application of experience / standard rules to scale up the reactor, etc., do not take into account the growth characteristics of microorganisms, and the existence of microorganisms Growth status mismatch and other issues

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