Towards new beta-lactam antibiotics.
Antibiotics have had a profound impact on human health and belong to one of the largest-selling classes of drugs worldwide. Introduced into industrial production only some half century ago, these miracle drugs have been the main contributors to the recent increase in human life expectancy. However, the accelerated emergence of bacteria that are resistant to multiple antibiotic types now appears as the most serious threat to continuing success in the treatment of infectious diseases. Recent advances in our knowledge of the structures and mechanisms of enzymes in the biosynthetic pathways of penicillins and cephalosporins, amongst the most important antibiotics in current use, have identified a common structural core together with common iron- and cosubstrate-binding motifs. The diversity in the catalytic specificities of these oxygenases using very similar structural platforms suggests that altering the substrate and product specificities of these enzymes should be possible in the laboratory. This opens up new avenues for industrial production and medical utilisation.
Andersson
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Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala Biomedical Centre. inger.andersson@molbio.slu.se
van Scheltinga
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Valegård
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D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018407:Bacterial Physiological Phenomena; D006801:Humans; D007501:Iron / Q000378:metabolism; D015394:Molecular Structure; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D018440:beta-Lactam Resistance / Q000502:physiology; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D007501:Iron; D010105:Oxygenases; D001618:beta-Lactamases