| Autor: |
Hojati Z; Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), Sackville Street, PO Box 88, Manchester M60 1QD, UK., Milne C, Harvey B, Gordon L, Borg M, Flett F, Wilkinson B, Sidebottom PJ, Rudd BA, Hayes MA, Smith CP, Micklefield J |
| Jazyk: |
angličtina |
| Zdroj: |
Chemistry & biology [Chem Biol] 2002 Nov; Vol. 9 (11), pp. 1175-87. |
| DOI: |
10.1016/s1074-5521(02)00252-1 |
| Abstrakt: |
The calcium-dependent antibiotic (CDA), from Streptomyces coelicolor, is an acidic lipopeptide comprising an N-terminal 2,3-epoxyhexanoyl fatty acid side chain and several nonproteinogenic amino acid residues. S. coelicolor grown on solid media was shown to produce several previously uncharacterized peptides with C-terminal Z-dehydrotryptophan residues. The CDA biosynthetic gene cluster contains open reading frames encoding nonribosomal peptide synthetases, fatty acid synthases, and enzymes involved in precursor supply and tailoring of the nascent peptide. On the basis of protein sequence similarity and chemical reasoning, the biosynthesis of CDA is rationalized. Deletion of SCO3229 (hmaS), a putative 4-hydroxymandelic acid synthase-encoding gene, abolishes CDA production. The exogenous supply of 4-hydroxymandelate, 4-hydroxyphenylglyoxylate, or 4-hydroxyphenylglycine re-establishes CDA production by the DeltahmaS mutant. Feeding analogs of these precursors to the mutant resulted in the directed biosynthesis of novel lipopeptides with modified arylglycine residues. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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