Vancomycin is a glycopeptide antibiotic with inhibitory effect on Gram-positive bacteria. Due to its special fermentation process, there are many factors that affect the fermentation of vancomycin, including carbon source, nitrogen source, temperature, pH and dissolved oxygen.
1. Carbon source
The carbon source plays a key role in cell supply and other aspects. Carbon source is not only a carbon source but also provides energy for growth and metabolism. Taking into account the actual application of production, and in order to increase the unit yield of fermentation, the optimization of the types of carbon sources becomes particularly important. In the process of carbon source optimization, it is necessary to understand the components of the carbon source in the formula and analyze whether different carbon sources play the same role. Through the unique carbon source experiment, a single investigation of multiple carbon sources was carried out, and the carbon sources that could promote the growth and resistance of bacteria were screened out, such as starch, dextrin, maltose, glucose, sucrose, soybean oil and glycerin. When the carbon source that promotes growth and metabolism is selected, a combination of various carbon sources can be investigated to obtain the highest fermentation yield. In the fermentation process, the requirements for bacterial growth and metabolites should be considered. In order to promote the growth of early bacterial cells, fast-utilizing carbon sources such as glucose and sucrose can be selected; and in order to produce antibodies and maintain the nutrition of the bacterial cells in the later period, slow-release carbon sources such as dextrin and starch can be used to achieve rapid and stable performance on fermentation to maximize yield. Glycerol, as a special factor in product synthesis, plays a key role in the fermentation process.
2. Nitrogen source
Nitrogen source belongs to the cell material of microbial cells and promotes the growth of cells. There are many sources of nitrogen, which can be divided into organic nitrogen sources and inorganic nitrogen sources.
Organic nitrogen sources include two types: quick-acting nitrogen sources, such as peptone, yeast extract powder, etc.; slow-release nitrogen sources, such as soybean powder, protein powder, yeast powder, etc. Compound organic nitrogen sources are often slow-release nitrogen sources, which contain more complex components. Some nitrogen sources also contain special growth factors or vitamins, which play a key role in increasing the yield of metabolites.
Inorganic nitrogen sources mainly include nitrate and ammonia. Inorganic nitrogen source is usually used as an auxiliary nitrogen source, but its role is also more critical. For example, ammonia water not only provides a source of N in the fermentation process, but also maintains pH.
In the entire process of biosynthesis of antibiotics, how to rationally and effectively utilize nitrogen sources to realize rational and orderly application is the key. The nitrogen source of vancomycin fermentation medium is divided into organic and inorganic. The organic nitrogen source has a more prominent integral effect. The specific nitrogen sources investigated are: soy peptone, yeast peptone, soybean protein powder, soybean powder, yeast powder, bran Flour and cottonseed meal. Experiments have found that yeast powder and gluten powder cannot be used by bacteria, while cottonseed meal and soybean protein powder can speed up the growth of bacteria, shorten the fermentation cycle, and shorten the antibiotic synthesis cycle, which improves the fermentation advantage. While peptones can promote the rapid growth of bacteria in the early stage of fermentation, the vigor of the bacteria is not enough in the later stage. Therefore, the selection of the medium can mix and match the fast-acting nitrogen source peptone and the slow-release nitrogen source cottonseed meal, and finally increase the potency.
To be continued in Part II…