Production of Recombinant Antibiotics

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Chapter: Pharmaceutical Microbiology : Recombinant DNA Technology

A large number of the antibiotics currently used have been isolated from the Gram-positive soil bacterium Streptomyces, although many other microorganisms have also been used as sources of antibiotics.


PRODUCTION   OF      RECOMBINANT      ANTIBIOTICS

 

A large number of the antibiotics currently used have been isolated from the Gram-positive soil bacterium Streptomyces, although many other microorganisms have also been used as sources of antibiotics. The biosynthesis of an antibiotic can sometimes include 10–30 separate enzyme-catalysed reactions, which makes the cloning of all the genes coding for these enzymes very difficult. A strategy used to isolate the complete set of antibiotic biosynthetic genes consists of the transformation of a recombinant gene library from an organism producing the antibiotic into a mutant strain of the same organism unable to produce it. The transformants can be screened for the production of the antibiotic by plating them on to agar plates that have been seeded with a sensitive bacterium. The appearance of halos of growth inhibition around the recombinant colonies indicates the successful cloning of the antibiotic biosynthetic gene cluster. This strategy was successfully used for the cloning and production of the antibiotic undecylprodigiosin from Streptomyces coelicolor, as illustrated in Figure 25.12.

 

 

In some instances, recombinant DNA technology has been successfully used to generate novel antibiotics by introducing in the same organism the genes responsible for the synthesis of two closely related antibiotics. By cross-feeding antibiotic precursors between two close metabolic pathways, novel antibiotics can be generated. This strategy has been very successful in the cross-feeding of antibiotic pathways between different Streptomyces spp.

 

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