A novel isoquinoline alkaloid, DD-carboxypeptidase inhibitor, with antibacterial activity isolated from Streptomyces sp. 8812. Part I: Taxonomy, fermentation, isolation and biological activities

Abstract

A novel isoquinoline alkaloid of molecular formula C10H9NO4, labeled JS-1, was isolated from the culture broth of Streptomyces sp. 8812. It was purified by acetone protein precipitation from the culture supernatant, followed by anion exchange and C18 RP HPLC columns. JS-1 is an inhibitor of exocellular DD-carboxypeptidases/transpeptidases (DD-peptidases) 64-575 II from Saccharopolyspora erythraea 64-575 II, and R39 from Actinomadura R39. JS-1 exhibits activity against Gram-negative bacteria, such as Bordetella bronchiseptica, Stenotrophomonas maltophilia, Proteus vulgaris, P. mirabilis, Burkholderia cepacia and Acinetobacter baumanii, with MIC values 10-160 microg ml(-1), and against Gram-positive bacteria, such as Staphylococcus aureus, with MIC values 40-206 microg ml(-1).