Two novel antibiotics, Sch 419558 and Sch 419559, produced by Pseudomonas fluorescens: effect on activity by overexpression of RpoE

• Published in: Bioorganic & medicinal chemistry 2004-06, Vol.12 (12), p.3333-3338
• Main Authors: Yang, Shu-Wei, Xu, Ling, Mierzwa, Ronald, He, Ling, Terracciano, Joseph, Patel, Mahesh, Gullo, Vincent, Black, Todd, Zhao, Wenjun, Chan, Tze-Ming, Chu, Min
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Applied microbiology; Bacterial Proteins; Biological and medical sciences; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - growth & development; Fundamental and applied biological sciences. Psychology; Gene Expression; Magnetic Resonance Spectroscopy; Medical sciences; Microbiology; Molecular Structure; Peptides; Pharmacology. Drug treatments; Pseudomonas fluorescens - chemistry; Pseudomonas fluorescens - metabolism; Sigma Factor - genetics; Sigma Factor - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.03.057

Two new RNA polymerase sigma-factor (RpoE) inhibitor, Sch 419558 ( 1) and Sch 419559 ( 2) were discovered from Pseudomonas fluorescens. Structures of 1 and 2 were elucidated by spectroscopic data analyses. Two new secondary metabolites designated as Sch 419558 ( 1) and Sch 419559 ( 2), were isolated from the fermentation broth of Pseudomonas fluorescens. Structure elucidation of 1 and 2 was accomplished by spectroscopic data analyses including MS and NMR experiments. Both compounds were identified as lipopeptides containing valine and threonine linked with 1-amino-1-hydroxy-heptadec-9-en-2-one or 1-amino-1-hydroxy-pentadecan-2-one carbon chains, respectively. Characterization of the amino acids was further confirmed by amino acid analysis. Compounds 1 and 2 exhibited antibacterial activity against a sensitized E. coli strain with minimum inhibitory concentration of 0.3 and 0.6 μg/mL, respectively. Overexpression of RpoE in the E. coli strain increased the MIC over 60-fold for compounds 1 and 2.