Fermentation process of vancomycin (II)

    1. Temperature and pH

    The growth and reproduction of bacteria and the synthesis of products are all based on the catalysis of enzymes, and the catalysis of enzymes is related to temperature and pH. Based on kinetic factors, how to control orderly becomes the key to research. In a certain range, the temperature value continues to increase, and the activity of the enzyme also increases. When it exceeds its maximum value, it will have a destructive effect on the enzyme itself. Therefore, it is necessary to do a good job in evaluating the reaction rate of the enzyme. During the fermentation process, the most suitable temperature for bacterial growth and product metabolism is likely to be inconsistent. Therefore, in the process of rate analysis, in order to avoid the influence of active factors, the entire fermentation process should maintain a suitable bacterial growth environment. Based on the optimal temperature, the application conditions should be determined in advance.

    1. Dissolved oxygen

    antibiotic-producing bacteria are mostly heterotrophic aerobic microorganisms. According to the growth and reproduction and the actual application of antibiotics, it is necessary to determine the amount of dissolved oxygen required by the bacteria. As the fermentation progresses, the amounts of bacteria increases, and the demand for oxygen of the bacteria gradually increases.

    Based on the strain itself, high-yielding strains and fermentation conditions are constantly changing, and antibiotic fermentation units are easily affected. Experiments have found that during the fermentation of Vancomycin, the mycelial state and the viscosity of the fermentation broth are different in different culture media, which causes different oxygen transfer, which ultimately affects the growth and metabolism of the bacteria. Therefore, based on the oxygen supply and ventilation of the equipment, a suitable medium can be selected according to the characteristics of the bacteria to improve the oxygen transfer of the fermentation broth.

    Dissolved oxygen concentration is a comprehensive parameter in the fermentation process. Based on the existing monitoring mechanism and management form, it is necessary to monitor the dissolved oxygen content of the entire fermentation process. Too high or too low dissolved oxygen will have adverse effects. Vancomycin can be synthesized normally only when the dissolved oxygen is sufficient. When the dissolved oxygen is insufficient, the assimilation of oxygen is insufficient to meet the energy required for vancomycin biosynthesis, which limits the production of products and reduces the fermentation of vancomycin. Dissolved oxygen is too low during the fermentation process, and the growth and metabolism of the bacteria are inhibited, which ultimately affects the yield of fermentation products. The high dissolved oxygen indicates that there are many problems in fermentation. First, the lack of nutrients leads to a decrease in oxygen consumption and a rise in dissolved oxygen. At this time, nutrients need to be supplemented; second, the viability of the bacteria itself is not enough, and the bacteria will age automatically. Dissolution leads to the release of substances, and a decrease in oxygen demand leads to a rise in dissolved oxygen. Therefore, it is very necessary to control the appropriate dissolved oxygen.


    [1] Ramakrishnan Nagarajan. Antibacterial activities and modes of action of vancomycin and related glycopeptides[J]. Antimicrobial agents and chemotherapy,1991(4):605-609.