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- W1978756072 abstract "The growing incidence of antibiotic resistance in bacteria poses a major public-health threat. Indeed, Gram-positive strains resistant to even vancomycin, previously the antibiotic of last resort, have appeared. In response to this threat, scientists have attempted to engineer new activities into old antibiotics. One approach has been to modify the non-ribosomal polypeptide synthetase (NRPS) pathways that are used to create peptide antibiotics, such as the penicillins and vancomycin. NRPSs are modular in structure, and the aim has been to swap modules between different pathways to create new antibiotic entities. However, the swapping process has been relatively inefficient, with low yields. In their paper, Gokhale et al.1 Gokhale R.S. et al. Dissecting and exploiting intermodular communication in polyketide synthases. Science. 1999; 284: 482-485 Crossref PubMed Scopus (292) Google Scholar demonstrate that the precise overall selectivity of the NRPSs depends on short intermodular peptide-linker sequences. Engineering new linkers should therefore allow more efficient module swapping and greater yields of new antibiotics. In an alternative approach, scientists have overcome vancomycin resistance by modifying the antibiotic’s carbohydrate chains. Ge et al.2 Ge M. et al. Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding d-Ala-d-Ala. Science. 1999; 284: 507-511 Crossref PubMed Scopus (320) Google Scholar provide evidence that these new entities work by a different method to vancomycin itself. Rather than binding to the terminal d-Ala-d-Ala peptide of cell-wall precursors, the modified analogues interact directly with bacterial proteins involved in the transglycosylation step of cell-wall biosynthesis. Thus, both papers provide vital new intelligence to the ground troops in the war against antibiotic resistance." @default.
- W1978756072 created "2016-06-24" @default.
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- W1978756072 date "1999-07-01" @default.
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- W1978756072 title "How new antibiotics are made and how they work" @default.
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- W1978756072 doi "https://doi.org/10.1016/s1357-4310(99)01517-8" @default.
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