Arylomycins A and B, New Biaryl-bridged Lipopeptide Antibiotics Produced by Streptomyces sp. Tue 6075. I. Taxonomy, Fermentation, Isolation and Biological Activities.

The Journal of Antibiotics
2002.0

Abstract

New lipopeptide antibiotics, colourless arylomycins A series and yellow arylomycins B series were detected in the culture filtrate and mycelium extracts of Streptomyces sp. Tu 6075 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics, which represent the first examples of biaryl-bridged lipopeptides. They show antibiotic activities against Gram-positive bacteria.In the course of ongoing research efforts aimed at exploring the biosynthetical potential of freshly isolated actinomycetes, the secondary metabolite profile of streptomycete strain Tu 6075 was subjected to a closer scrutiny. HPLC-diode-array analysis (HPLC-DAD) coupled with HPLC-electrospray-mass-spectrometry (HPLC-ESI-MS) revealed a pattern of metabolites in the extracts from the culture filtrate and mycelium that could not be identified by means of our HPLC-UV-Vis-Database2). The database contains about 700 reference compounds, most of which are antibiotics. Two series of homologous metabolites with retention times between 9.0 and 11.4 minutes were produced by strain Tu 6075, having end-absorption in the UV range and a side-maximum at 290 and 295nm, respectively. The spectra showed a high conformity with reference compounds of the peptide sub-library stored in the HPLC-UV-Vis-Database. Analysis by HPLC-ESI-MS resulted in molecular masses of 838 and 883 Da for two major components of arylomycins A and B series, respectively.This report deals with the taxonomy of the producing strain, fermentation, isolation and biological activities of arylomycins. Investigations on their chemical structures are reported in the subsequent paper3). These results indicated that colourless arylomycins A series are lipopeptide antibiotics with a unique biaryl bridge between N-methyl-4 hydroxyphenylglycine5 (MeHpg5) and tyrosine7 in their hexapeptide backbone. In the cases of yellow arylomycins B series, tyrosine7 in A series is replaced by 3-nitrotyrosine7. Their structures are shown in Fig. 1.

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