Novel Lipopeptides, Kiostostatins A-E from a Marine-Derived Bacterium Bacillus subtilis

Abstract

As part of our continuing interest to discover secondary metabolites from marine sponge and sediment derived bacteria, a bacterial strain 109GGC020 showing good antimicrobial activity was isolated from a marine sediment sample collected from Gageocho, Republic of Korea. The bacterium was identified by 16s rRNA sequence analysis as Bacillus subtilis. After 7 days fermentation of the strain in optimum growth condition, five linear lipopeptides, kiostostatins A-E (1-5), were isolated using chromatographic procedures. These lipopeptides were characterized by extensive 1D, 2D and high resolution ESIMS data analysis and their stereoconfigurations were assigned by chemical derivatization studies. The minimum inhibitory concentrations (MICs) of kiostostatins 1-5 were evaluated against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) and fungi (R. solani, B. cinerea and C. acutatum) by broth dilution assay. Kiostostatins exhibited antibacterial and antifungal activity with MICs values of 0.003-0.022 μM. These results demonstrated 1-5 as potent antibiotics and fungicides. Furthermore, kiostostatins 1-5 displayed cytotoxicity against six human cancer cell lines with GI50 values of 0.01-0.04 μM.m Gageocho, Republic of Korea. The bacterium was identified by 16s rRNA sequence analysis as Bacillus subtilis. After 7 days fermentation of the strain in optimum growth condition, five linear lipopeptides, kiostostatins A-E (1-5), were isolated using chromatographic procedures. These lipopeptides were characterized by extensive 1D, 2D and high resolution ESIMS data analysis and their stereoconfigurations were assigned by chemical derivatization studies. The minimum inhibitory concentrations (MICs) of kiostostatins 1-5 were evaluated against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) and fungi (R. solani, B. cinerea and C. acutatum) by broth dilution assay. Kiostostatins exhibited antibacterial and antifungal activity with MICs values of 0.003-0.022 μM. These results demonstrated 1-5 as potent antibiotics and fungicides. Furthermore, kiostostatins 1-5 displayed cytotoxicity against six human cancer cell lines with GI50 values of 0.01-0.04 μM.