Production of antibiotics

The production of antibiotics has been widespread since the pioneering efforts of Floreyand chainin 1939. The importance of antibioticsto medicinehas led to much research into discovering and producing them.

Identifying useful antibiotics

Image:Agar plate with colonies.jpg Despite the wide variety of known antibiotics, less than 1% of antimicrobial agents have any medicalor commercial value. The most commonly known antibiotic, Penicillinhas a highly selective toxicityand therapeutic index(as eukaryotic animal cellsdo not contain peptidoglycan, they are usually unaffected by it). This is not so for many antibiotics. Others simply lack advantage over the antibiotics already in use, or have no other practical applications.

In order to identify the useful antibiotics, a process of screening is often employed. Using this method, isolates of a large number of microorganismsare culturedand then tested for production of diffusible productswhich inhibit the growth of test organisms. However, the majority of the resulting antibiotics are already known and must therefore be disregarded. The remainders must be tested for their selective toxicities and therapeutic activities, and the best candidates can be examined and possibly modified.

A more modern version of this approach is a rational design program. This involves screening being directed towards finding new natural products that inhibitspecific targets (e.g. a particular step of a metabolic pathway) on microorganisms, rather than tests to show general inhibition of a culture.

Industrial production techniques

Antibiotics are produced industrially by a process of fermentation, where the source microorganism is grown in large containers (100-150,000 litres or more) containing a liquid growth medium. Oxygen concentration, temperature, pHand nutrientlevels must be optimal, and are closely monitored and adjusted if necessary. As antibiotics are secondary metabolites, the population size must be controlled very carefully to ensure that maximum yield is obtained before the cells die. Once the process is complete, the antibiotic must be extracted and purifiedto a crystallineproduct. This is simpler to achieve if the antibiotic is soluble in organic solvent. Otherwise it must first be removed by ion exchange, adsorptionor chemical precipitation.

Strains used for production

Microorganisms used in fermentation are rarely identical to the wild type. This is because species are often genetically modifiedto yield the maximum amounts of antibiotics. Mutationis often used, and is encouraged by introducing mutagenssuch as ultraviolet radiation, x-rays or certain chemicals. Selection and further reproductionof the higher yielding strains over many generations can raise yields by 20-fold or more. Another technique used to increase yields is geneamplification, where copies of genes coding for proteinsinvolved in the antibiotic production can be inserted back into a cell, via vectors such as plasmids. This process must be closely linked with retesting of antibiotic production and effectiveness.

References

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This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Production+of+antibiotics Wikipedia article Production of antibiotics.