Structural characterization of a lipopeptide antibiotic A54145E(Asn 3 Asp 9) produced by a genetically engineered strain of Streptomyces fradiae

Abstract

A potent new lipopeptide antibiotic, A54145E(Asn 3 Asp 9), was isolated from the fermentation broth of Streptomyces fradiae DA1489 engineered to delete genes encoding enzymes involved in hydroxylation of Asn 3 and methoxylation of Asp 9. The chemical structure predicted from the genetic changes in the biosynthetic pathway was determined by analyses of chemical transformations, D, L-amino acid quantitation by enantiomer labeling, tandem LC-MS/MS and 2D NMR techniques. These studies confirmed the primary amino acid sequence of A54145E(Asn 3 Asp 9) predicted from the genetic engineering strategy, and also confirmed the structure and locations of three D-amino acids predicted from bioinformatic studies. © 2011 Japan Antibiotics Research Association All rights reserved.