Microbial Fermentation Pharmaceuticals

1, the discovery of antibiotics
1928, British bacteriologist Fleming B discovered the antibacterial substance penicillinIn the 1940s, 14 antibiotics were discovered, more than 20 were discovered in the 1950s, and the synthetic and semi-synthetic antibiotic phases of chemical structural modification began in the 1960sAt present, about 9000 kinds of antibiotics, semi-synthetic antibiotics are found and isolated to about 1000 kinds, a total of more than 10,000 speciesBut the actual production and application of only more than 100 kinds2, fermentation pharmaceutical typefermentation: the process of obtaining the product through microbial cultureOften used to explain the product, crowned with a certain fermentation, such as penicillin fermentation, vitamin fermentation and so onFermentation engineering on-demand oxygen is divided into aerobic fermentation and anaerobic fermentation(1) Microbial bacteria fermentationmicrobial bacteria fermentation is for the purpose of obtaining microbial bacteria, such as: bread yeast fermentation, single-cell protein fermentation (using a variety of carbon sources), fungi (various mushrooms, winter worm summer grass), biological control agent (Suyunjinx, with spore crystals can kill scales, winged insects)(2) Microbial enzyme fermentationmicrobial enzyme fermentation is fermentation for the purpose of obtaining enzymes, such as penicillin incarnate enzymes, used in semi-synthetic penicillin, the preparation of intermediate 6-aminomyneane acid(3) Microbial metabolites fermentation(1) primary metabolites: amino acids, nucleotides, vitamins, organic acids(2) secondary metabolites: the most important is antibiotics(4) Microbial conversion fermentationusing one or more enzymes of microorganisms to transform a compound into a structurally related more valuable product of biochemical reaction into transformation fermentation3, the types of pharmaceutical microorganismsthe production of drugs of natural microorganisms mainly include bacteria, line bacteria and filament fungi three categoriesBacteria mainly produce cyclic or stinky polypeptide antibiotics, such as Bacillus, which produces bacitracin, bacillus polymyxa, which produces colistin and polymyxinBacteria can also produce amino acids and vitamins, such as Brevisum flarum, which produces glutamate, and large and small bacterialine bacteria mainly produce various types of antibiotics, to streptomycin genus the most, Noca genus is less, there are small monospores genusThe main antibiotics produced are amino glycin (streptomycin, neomycin, carnamycin, etc.), tetracycline (tetracycline, jinmycin, tomycin, etc.), line-inmycin (linemycin D) large ring esters (erythromycin, helixmycin, column-crystalmycin) and polyene large cyclomycin (mycomycin, anti-dythromycmycin, etc.)Acid, alkaline and neutral, but mostly alkalinethe fungi of the genus oxycotoxin, penicillin genus produced penicillin and gray jaundice, cephalosporine genus produced cephalosporine and so onLipid ring aromatic or simple oxygen heterocyclic class, mostly acidic compounds4, the basic process of fermentation pharmaceuticalfermentation pharmaceutical is the use of pharmaceutical microorganisms, through fermentation culture, under certain conditions, growth and reproduction, while in the metabolic process to produce drugs, and then, from fermentation liquid extraction separation, purification refining, obtain drugsThe three main segments of the strain selection (mutation and selection breeding), fermentation and extraction (isolation and purification) are the three main segments of fermentation pharmaceuticalThe main process is as followsprocess consists of two stages: fermentation and separation purificationthe selection and preservation of the production of strains: the selection of bacteria to increase the output of penicillin from the initial 20 units to more than 80,000 unitsGood strains should be high-yield, stable performance and easy to cultivate fermentation stage includes production of bacteria, spore preparation, seed preparation, fermentation culture, is the biological processing engineering process spores preparation: preserved strains, resuscitated on solid media, and growth produces spores seed preparation: the prepared spores are attached to a shaker or small fermentation tank, cultured, and the spores germinate and reproduce For large-scale fermentation, 2 expanded culture preparation seeds are widely used, and finally connected to the fermentation tank fermentation: the seeds are connected to the fermentation tank in a certain proportion, and the cultivation is the key stage and process of the production of drugs Ventilation, stirring are required to maintain the appropriate temperature and tank pressure Fermentation has a certain period of time During, sampling analysis, aseptic inspection, yield determination Add defoaming agents, acid-base control pH, supplement carbon sources, nitrogen sources and precursors to promote yield separation purification stage includes fermentation liquid treatment and filtration, separation extraction, refining, finished product inspection, packaging, factory inspection, is the process of chemical separation engineering pre-treatment and filtration of fermentation fluid: the protein and impurities in the fermentation liquid are precipitated, the filter flow rate is increased, and the mycelium is separated from the fermentation solution Such as mycomycin, gray myomycin, cyclomycin, erythromycin drugs are present in mycelium, to be extracted from the bacteria If present in the filtor, clarify the filtlot and extract it further extraction and refining: adsorption, precipitation, soy medium extraction, ion exchange, etc extract the drug from the filter Refining is the further purification and production of concentrated or coarse products Four basic methods can be repeated or cross-used finished product test: including characteristics and identification test, safety test, buck test, heat source test, aseptic test, acidity test, price determination, moisture determination and so on finished packaging: qualified finished products for packaging, for raw materials The preparation shall be re-assembled by the preparation workshop or factory