Antibiotics and regulation of metabolism

Antibiotics biosynthesis occurs when N2 sources are completely depleted from the medium. This will decreases the rate of TCA cycle because part of its intermediates and energy are not used for amino acids and protein biosynthesis.

Under this conditions some microorganisms accumulate citric acid which cause a decrease in the levels of Acetyl CoA.

Another possibility is that accumulated Acetyl CoA is then used to synthesize fatty acids and polyketaides. Increase of Fatty acids synthesis will slow down their further synthesis and increase the polyketide synthesis

Polyketides They are secondary metabolites that are found in number of antibiotics. They are produced by polyketides Synthases in a process similar to fatty acids synthesis. Both are synthesized through linear chain elongation by addition of 2 carbon units. Polyketides exhibit antibacterial properties.

Unbalanced growth hypothesis In microorganisms when balanced growth is disappear, primary metabolites accumulate due to their overproduction. These primary metabolites are converted into secondary metabolites that are excreted from the microbial cells.

How do antibiotic- producing microorganism avoid suicide? Some antibiotics e.g: Penicillin and cyclosporin are excreted from cells against gradients.

continued In some cases, it has been demonstrated that appropriate target structures, reactions or molecules are absent or not employed by the antibiotic-producing microorganisms. e.g: The respiratory chain complex targeting by actinomycin A is absent in Streptomycetes antibioticus.

Continued Some antibiotics have ribosomes with very low or no affinity to their own antibiotics. E.g: S. griseus has no affinity to erythromycin. They could protects itself against its own antibiotic by methylation of 23 S of its 50 S ribosomal subunits which results that the antibiotic fails to bind ribosomes.

Continued In some cases, the drug may be modified and inactivated. e.g: Various actinomycetes [roducing aminoglycoside antibiotics are able to be: -Adenylylated -Phosphorylated -Acetylated

Continued Some antibiotic producer protect themselves by the production of metabolite that inactivate their own antibiotics. e.g Cystein inactivated several antibiotics like penicillin and streptomycin.