Production and characterization of monochlorinated and dechlorinated A40926 derivatives

Nonomuraea sp. ATCC 39727 is the producer of the A40926 complex of lipoglycopeptide antibiotics which contain chlorine atoms in amino acids 3 and 6 of the peptide backbone. Using a classical mutagenesis and selection approach we have isolated a Nonomuraea sp. ATCC 39727 mutant strain able to direct production towards new A40926 analogues dechloro-A40926 (DDC) lacking two chlorine atoms and the two monochloro-A40926 (MDC1 and MDC2) that are not produced fermenting the wild type strain. Dechlorinated A40926 derivatives were obtained in considerable amount in a standard fermentation process and were purified and chemically characterized. The dechlorinated A40926 derivatives DDC and MDC2 showed improved antimicrobial activity against coagulase negative staphylococci strains in respect to A40926 complex. Dechlorinated derivatives of the related antibiotic teicoplanin are also reported in the literature and are generally less active than the parental products.