This presentation about the glance of industrial production and application of antibiotics useful for learner who quikly understand the antibiotics production and their uses.
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GOVT. V.Y.T.P.G. AUTONOMOUS COLLEGE DURG, (C.G .) INDUSTRIAL PRODUCTION OF ANTIBIOTICS PRESENTED BY- B.R. ADITYA M.Sc. FINAL BIOTECHNOLOGY Seminar on
Introduction Antibiotics are chemical substance that can kill microorganisms or inhibit their growth and are therefore used to fight infections in human or animals. Most of the antibiotics are produced by microorganism. Certain semi-synthetic antibiotics are the chemically modified natural antibiotics.
history It was in 1928 Alexander Fleming made an accidental discovery, that the fungus Penicillium notatum , produced compound that selectively killed a wide range of bacteria without adversely affecting the host cells. The penicillin discovery of Fleming has revolutionized antibiotics research.
Production of antibiotics a major pharmaceutical industry The commercial production of antibiotics is a highly profitable industry world over. Annual sales of antibiotics will run into billions of dollars with an annual growth potential of about 10%. Antibiotics may be produced by microbial fermentation or chemical synthesis or a combination of both. For certain antibiotics the basic molecule is produced by fermentation and its therapeutic value can be increased by chemical modification.
penicillin's Penicillin's are a group of β - lactam containing bactericidal antibiotics. The basic structure of all penicillin's consists of a lactam ring and a thizolidine ring fused together to form 6-amino penicillanic acid.
Action of penicillin Natural penicillin are effective against several gram positive bacteria. They inhibit the bacterial cell wall synthesis and causes cell death. Natural penicillin are ineffective against microorganisms that produced β - lactamase . Since this enzyme can hydrolyse penicillin e.g. staphylococcus aureus . Several semi-synthetic penicillin's that are resistant to β - lactamase have been developed &successfully used against a large no. of gram negative bacteria. e.g. cloxacillin,ampicillin .
Organism for penicillin production In early days Penicillium notatum was used for the large scale production of penicillin's. Currently Penicillium chrysogenum and its improved mutant strains are preferred. One of the high yielding strains wis Q176 is produced by several penicillin manufacturers .
Biosynthesis of penicillin L- α amino adipic acid L- cysteine L- α amino adipyl cysteine L- valine α -L amino adipylcysteinyl valine Isopenicillin N Phenyl acetyl co A acyltransferase α AAA + Co A Penicillin G
Production process of penicillin
recovery As the fermentation is complete the broth containing about 1% penicillin is processed for extraction. The mycelium is removed by filtration. Penicillin is recovered by solvent (n-butyl acetate or methyl ketone extraction at low tem.(<10c)acidic pH (<3.0) By this the chemical enzymatic degradation of penicillin can be minimized. The penicillin containing solvent is treated with the activated carbon or remove impurities. Penicillin can be removed by adding potassium or sodium acetate.
amino glycosides/ streptomycin Amino glycosides are oligosaccharide antibiotics. They contain an amino acylhexanol moiety which is bound to other amino sugar by glycosidic linkages . More then 100 amino glycosides are known e.g. streptomycin, neomycin, kanamycin, gentamycin , etc. Amino glycosides are very potent antibiotics and act against gram positive and gram negative bacteria besides mycobacterium.
organism Amino glycosides organisms Streptomycin Streptomyces griseus Neomycin B &C S. fradiae Kanamycin A,B and C S. kanamyceticus Hygromycin B S.hygroscopicus Gentamicin Micromonospora purpurea Sisomicin M . inyoensis
Production process &recovery The medium used for streptomycin usually consists of soy meal or soy flour or corn syrup that can supply glucose at a slow rate. The initial supply of Nitrogen NH 3 phosphate is also obtain from soy meal. Temperature at 27-30 pH 6.5-7.5. Aeration rate 0.5-10vvm
recovery Streptomycin or another amino glycosides are the basic in nature. They can be recovered by weak cationic exchange resins in an ion exchange column. Treatment with activated carbon is often necessary to remove impurities streptomycin can be precipitated in the form of surface salt.
tetracycline Tetracycline's are broad spectrum antibiotics with widespread medical use. They are effective against gram positive bacteria and gram negative bacteria besides other organisms. They are most commonly used antibiotics next to cephalosporin's and penicillin's. Tetracycline's inhibit protein biosynthesis by blocking the binding of aminoacyl t-RNA to ribosomes .
biosynthesis
Inoculums (spores) preservation Pre fermenter fermenter Mycelium removal Shake flask Agar plates Recovery and production
recovery At the end product of the fermentation, the culture broth is filtered to remove the mycelium. The filtrate is treated with n- butanol or methylisobutylketone in acidic or alkaline condition for extracting the antibiotics. I is then absorbed to activated charcoal to remove other impurities.