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APIs production through microbial fermentation

  • There are many microorganisms in the world, and these microorganisms play a very important role in human life. At present, the most extensive application field of microorganisms is pharmaceuticals. With the help of the microbial fermentation, many drugs that are beneficial to human health can be produced.

     

    The history of using fermentation of microorganisms to make medicine can be traced back to 1796, when British doctor E. Jenner used vaccinia vaccination to prevent smallpox and succeeded. By the end of the 19th century, L. Pasteur. P.Enrich and Von Rehiring have successively invented vaccines and toxoids to prevent or treat various bacterial infectious diseases. Since then, research on the use of microorganisms to produce vaccines has developed vigorously. In 1928, Fleming discovered penicillin by accident, but people believed that the results of animal experiments could not guide human medical practice. At the beginning of World War II, with the deepening of people's understanding of the importance of antibiotics, especially penicillin, the development of microbial fermentation for pharmaceuticals was greatly promoted.

     

    The use of microbial fermentation to produce drugs must be completed by fermentation engineering. The pioneering research of fermentation engineering technology and its successful application in the production process provided new concepts and models for the production of penicillin in the 1940s, and subsequent production of drugs by microbial fermentation and even fermentation engineering. At the same time, fermentation engineering technology has also stimulated research on amino acid fermentation, vitamin fermentation, and enzyme preparations.

     

    According to different chemical characteristics, the drugs produced by microbial fermentation can be classified into the following six categories:

    1. Antibiotics

    Antibiotics, such as Ansamitocin P-3 and Mitomycin C, are secondary metabolites and their derivatives that can inhibit or affect the life process of the living organism at low concentrations. Antibiotics that have been discovered are anti-bacterial, anti-tumor, anti-fungal, anti-viral, antiprotozoal, anti-algae, anti-parasitic, insecticidal and anti-cytotoxic antibiotics. According to statistics, since the 1940s, the total number of known antibiotics is no less than 9,000, and their main source is microorganisms, especially soil microorganisms, which account for about 70% of all known antibiotics.

    1. Amino acids

    At present, amino acid drugs are divided into individual amino acid preparations and compound amino acid preparations. The former is mainly used to treat certain targeted diseases. For example, arginine is used to treat hepatic coma, photonine is used to fight allergies, hepatitis and leukopenia, and methionine is used to prevent hepatitis, liver necrosis, and fatty liver. While compound amino acid preparations mainly provide raw materials for synthetic protein for critically ill patients to supplement the lack of protein intake in the digestive tract.

    1. Nucleotides

    Nucleotide drugs produced by the microbial fermentation process include inosinic acid, inosine, 5-adenosine (AMP), adenosine triphosphate (ATP), flavin adenine dinucleotide (FAD), coenzyme A (CoA), Coenzyme I (C01), etc.

    1. Vitamins

    The vitamin drugs produced by microbial fermentation include 2-keto-gulonic acid (the raw material of vitamin C), ergosterol, vitamin B2 (precursor of vitamin D2), Vitamin B12 (Diamenine) and so on.

    1. Steroid hormones

    In the production process of steroid hormones, some specific transformation reactions require the action of microorganisms.

    1. Medicinal enzymes

    Medicinal enzymes mainly include digestive enzymes, anti-inflammatory enzymes, cardiovascular disease treatment enzymes, anti-tumor enzymes and other enzymes. Many of these medicinal enzymes can be produced by microbial fermentation, such as protease, cellulase, lipase, streptokinase, urea kinase, asparaginase, superoxide dismutase, etc.

     

    In recent years, research on fermentation technology and its control has also been developed. The use of computer online control and immobilized cell technology has brought new development space for the microbial fermentation pharmaceutical industry.