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 C 10 H 9 NO 4 , 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 lg ml À1 , and against Gram-positive bacteria, such as Staphylococcus aureus, with MIC values 40-206 lg ml À1 .

Characterization and Optimization of Biosynthesis of Bioactive Secondary Metabolites Produced by Streptomyces sp. 8812

“…Both compounds exhibit antibacterial properties, have the ability to inhibit dd-carboxypeptidase 64-575 activity and are stable to β-lactamase activity. Their chemical structures may serve as lead compounds for modifications enhancing their biological activities (Solecka et al, 2009a;2009b;2012a;2012b).…”

N-acetyl-3,4-dihydroxy-L-phenylalanine, a second identified bioactive metabolite produced by Streptomyces sp. 8812

“…To examine the specificity spectrum of the JS-2 compound, inhibition assays were performed for a range of common proteolytic enzymes: pancreatic elastase (type IV) from porcine pancreas, carboxypeptidase A from bovine pancreas, trypsin from porcine pancreas, and papain from Papaya latex, according to the procedures described in our previous paper, 3 and leucine aminopeptidase (type IV-S) from porcine kidney microsomes as reported by Cahan et al 14 It was determined that at a concentration of 1.4 mM, the JS-2 compound causes 50% inhibition of carboxypeptidase A, whereas the rest of the enzymes remained active at higher concentration, 1.84 mM.…”

“…For assessment of genotoxicity, two genetically modified Bacillus subtilis strains, M45 rec À and H17 rec + , obtained from Dr Yoshito Sadaie (Department of Induced Mutation, National Institute of Genetics, Shizuoka, Japan) were examined by the disc-diffusion method according to Kada's procedure. 3,16 The JS-2 compound did not inhibit the growth of the tested B. subtilis strains; hence, it was determined as nongenotoxic.…”

New Derivatives of 3,4-Dihydroisoquinoline-3-carboxylic Acid with Free-Radical Scavenging, D-Amino Acid Oxidase, Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activity

“…8812 fermentation process [8,9]. This prompted us to prepare a series of hydroxy-and halogeno-substituted 3,4-dihydroisoquinoline-3-carboxylic acids and investigate their biological activity.…”