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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