ANTIBIOTICS

The term antibiotics means a chemical substance, derived from microorganisms, which has the capacity of inhibiting growth and even destroying other microorganisms in dilute solution. Antibiotics are a heterogeneous group of bioactive molecule with different structures and modes of action. Certain microbes synthesize antibiotics as a consequence of inborn errors of their metabolism which are sometimes encountered in mutants.

Over 4500 different antibiotics have been recorded so far, but only some 100 have been widely used to treat human, animal and plant diseases. The genus Streotomyces is the source of over one half of the known antibiotics ,the other being derived from Micromonospora ,Actinomadura,Actinoplanes Nocardia,Certain other ctinomytycycetes,Pencilliln,Cephalosporium ,Bacillus and few other microbes.

Antibiotics mainly Penicillin and cephalospoium are of tremendous clinical importance, some of them have abroad spectrum activity against several different pathogens where as others are effective only against some particular type of pathogens .diverse antibiotics have also been used in agriculture and pesticides. Some antibiotics may also show antiviral, cytotoxic or antitumor activities .others are being increasingly used against helminthes, protozoa o other organisms.
Several years ago, naturally produced antibiotics were being used ,but now they are being synthesized .following isolation of the penicillin nucleus ,6 amino pencilliinic acid (6 APA ) semi synthetic penicillin have been made by attaching different side chains to 6-APA.

Most programmes of industrial antibiotic production involve some screening trials to isolates new producer organisms either from natural habitats or from established cultures by mutagenesis or recombination. Protoplast fusion and the use of recombinant DNA techniques have made it possible to insert useful genetic properties directly into the selected organisms.

FOLLOWING ARE THE STEPS FOR A GOOD STRAIN DEVELOPMENT STRATEGY.

• induction of genetical or ecological variations
• preselection
• Testing of the selected strains on pilot plant scale
• Introduction on production scale in the main plant

Recent researches have indicated that Streptomyces,the genes that encode for enzymes involved in antibiotic production are located in clusters on the chromosome or plastids Transformation of the protoplasts with plasmids DNA and transfection with bacteriophage involve DNA uptake .This step is then followed by regeneration of at least some of the protoplasts which have been successfully transformed or transfected .In this way Gil and Hopwood in 1983 could successfully clone specific determining antibiotic biosynthesis ,and these genes have been expressed both in Streptomyces and E.Coli.

ANTIBIOTIC FERMENTATION

The major objective in antibiotic fermentation is to minimize production costs by optimizing the fermentation and recovery process and by using well tested improved microbial strains.
Cultures of Penicllium Notatum,P Chrysogeum, and several other molds produce penicillin and the antibiotic yield can be greatly increased if the fermentation medium is supplemented with such organic substances as casein, yeast extract and meat products. Corn steep liquor is a suitable substrate for P.Chrysogenum to produce good amounts of Pencillin.To obtains high antibiotic yields, the PH in the fermenter is maintained between 6.8 and 7.4 and temperature about 25 degrees by proper control of agitation and aeration.

Three mycelia fungi via, Claviceps Purpurea,Penicllium Chrysogenum and Streptomyces Aureofaciens have been immobilized in calcium alginate beads for sustained production of ergot alkaloids, Penicillin and Chlorotetracyclin, respectively. The formation of pallets from free mycelia of penicllium is necessary for the production of pencillin.Immolization induces a state of pellating and hence stimulates penicillin synthesis in C.Pupurea; the immobilization technique is conductive to sustained production of ergot alkaloids over a longer period of time as compared to free mycelia.
Of the clinically useful pencillins, penicillin G and penicillin V are made by fermentation and their resistance to staphylococcal pencillinase is virtually nil. Most other penicillin's are produced by semi synthetic methods of these amoxicillin, ampicllin ,epicillin ,metamacillin and proppicllin exemplify those pencillins which show a low resistance to staphylococcal pencillinase ,whereas cloxacillin ,cyclacillin,methicllin, and oxacillin show a fairly high resistance.
Amongst the clinically important tetracyclines, 6 - deoxy - 5- oxytetracycline and & - dimethylamino -6 -deoxy-6dimethy -tetracycline are produced synthetically whereas tetracycline, 7-chlorotetracyccline, and 5-oxytetracycline are produced by fermentations, culture of Streptomyces Aureofaciens, S.antibioticus. S.aurens, S.flavus, S.parvus, and other species are employed .some of the most potent tetracycline producers have been isolated by mutagenesis. The fermentors are usually loaded with appropriate concentrations of sucrose and zinc sulphate.some other substrates are peanut oil meal and molasses.

Bacitracin is produced microbially from a variety of raw materials such as tryptone meat broth, soya bean meal, starch, and calcium lactate and cottonseed meal. These media are used in surface or submerged cultures and yields of bacitracin of up to 400 units /ml can be obtained after an incubation period of 30 hours.

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