title: Auxotrophic-precursor directed biosynthesis of nonribosomal lipopeptides with modified tryptophan residues.
abstract: Feeding 5-hydroxy and 5-fluorotryptophan to a Streptomyces coelicolor Trp-auxotrophic strain WH101 results in the production of a number of new calcium-dependent antibiotics (CDAs) possessing modified Trp residues. It is anticipated that this method could be used to modulate the biological properties of Trp-containing nonribosomal peptide natural products, or to generate analogues with useful fluorescent properties for studying biological mechanisms of action.
authors.affiliation: School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, UK.
authors.forename: Bagher
authors.initials: B
authors.lastname: Amir-Heidari
authors.forename: Jenny
authors.initials: J
authors.lastname: Thirlway
authors.forename: Jason
authors.initials: J
authors.lastname: Micklefield
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D008074:Lipoproteins / Q000096:biosynthesis*; D015394:Molecular Structure; D046908:Peptide Biosynthesis, Nucleic Acid-Independent / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D008074:Lipoproteins; D010455:Peptides; C026927:5-fluorotryptophan; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D002118:Calcium