| Popis: |
Antibiotics are synthesized by dedicated gene products; they are anything but accidents. All the structural genes required for tylosin biosynthesis are probably present in the cluster, but additional regulatory genes might well be located elsewhere in the genome. Antibiotic-biosynthetic gene clusters commonly include ‘‘pathway-specific’’ regulators. These typically encode transcriptional activators that turn on the structural genes for antibiotic production. Antibiotic-producing organisms are typically resistant to their own toxic metabolite(s), and some of the strategies employed for self-protection are discussed below and elsewhere. Such resistance is usually quite specific for the avoidance of suicide; across-the-board resistance is not common. The fungus that produces penicillin is not faced with any particular problem as a result of doing so, since fungal cell walls do not contain peptidoglycan. On the other hand, actinomycetes that produce antibacterial compounds pose an interesting challenge for themselves. Such strains can adopt either of two resistance strategies in order to avoid suicide. Studies with puromycin and chloramphenicol revealed that peptidyltransferase activity has to do with the larger ribosomal subunit, whereas tetracycline blocked aminoacyl-tRNA binding to the ribosome mRNA complex from a site on the smaller subparticle. The convergence of these various approaches will reveal in molecular detail how antibiotics block conformational transitions that underlie ribosomal function. The ribosome continues to be a focus for the application of ground-breaking methodology to biological systems, and enigmatic small molecules still contribute to our enlightenment. |
