The nonribosomal peptide biosynthetic system--on the origins of structural diversity of peptides, cyclopeptides and related compounds.
A variety of peptides have been detected in microorganisms. Some have found applications in various fields, for example the classical beta-lactam antibiotics, immunosuppressors like cyclosporin, promising new antibacterials like teichoplanin or daptomycin and antifungals like echinocandin. For none of these has it been established how their complicated biosynthetic pathways have evolved or what functions they fulfill within or for their producers. So it is unclear what selection processes limit the range of their structural analogues within various groups of microorganisms. We here consider recent data in the field of biosynthesis and how they may suggest mechanisms of genetic diversity. These may illustrate the complexity of genetic and intracellular organization of biosynthetic pathways and indicate the cellular context of some metabolites related to the complex background of the production of each metabolite. Research focusing on various targets like the increase of productivity of fermentations or the spread of resistances to antibacterials is slowly being understood.
Kleinkauf
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Institute of Biochemistry and Molecular Biology, Technical University Berlin, Germany.
von Döhren
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D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry; D001407:Bacillus / Q000235:genetics / Q000378:metabolism; D005075:Biological Evolution; D006096:Gramicidin / Q000096:biosynthesis / Q000737:chemistry; D007769:Lactams; D008969:Molecular Sequence Data; D010407:Penicillium / Q000235:genetics / Q000378:metabolism; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D017262:Siderophores / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
D000900:Anti-Bacterial Agents; D007769:Lactams; D010455:Peptides; D010456:Peptides, Cyclic; D017262:Siderophores; D006096:Gramicidin