Bioactive constituents from marine Bacillus strains

Abstract

In the course of our investigation on bioactive substances from marine microorganisms, the strains of gram-positive rod-shaped bacteria, Sc018 and Sc026 from marine sediment and Sc004 from seawater around Sichang Island showed interesting biological activity. Based on morphological, cultural, physiological and biochemical characteristic studies, the strains Sc018 and Sc026 were identified as belonging to the genus Bacillus, while the strain Sc004 was still unable to be identified. Directed by anti-herpes simplex virus activity, fractionation of the butanol extract from the broth of the strain Sc004 yielded a known diketopiperazines (DKPs), cyclo-(L-Pro-Gly) and a known purine nucleoside, 2-deoxyadenosine; meanwhile the dichloromethane extract from the strain Sc018 yielded three DKPs including two known compounds, cyclo-(trans-4-OH-L-Pro-L-Phe) and cyclo-(D-Pro-Leu), and one new compound, cyclo-(D-Pro-Ile). The bioassay directed fractionation, using antibacterial activity against both Staphylococcus aureus and Bacillus subtilis, of the ethylacetate extract from the fermentation broth of the strain Sc026 led to the isolation of five DKPs including four known compounds, cyclo-(L-Pro-Gly), cyclo-(L-Pro-D-Leu), cyclo-(L-Pro-L-Trp), and cyclo-(D-Pro-L-Trp) and a new compound, cyclo-(D-Pro-L-Phe), together with a new cyclic tetrapeptide, cyclo-(4-OH-Pro-4-OH-Pro-Leu-Phe). Three macrolactins including the known macrolactin F, along with two new compounds, 7-O-succinyl macrolactin F and 7-O-succiny1 macrolactin A were also obtained from the strain Sc026. The chemical structures and relative stereochemistry of the compounds were elucidated through extensive analyses of their IR, MS, 1H, and 13C NMR spectral data, especially 1D-and 2D-NMR, as well as comparison with known related compounds. All of these DKPs showed new activity against Herpes simplex virus while 2-deoxyadenosine exhibited weak antimalarial activity. The isolated macrolactins exhibited both anti-herpes simplex virus activity and antibacterial activity against S. aureus and B.subtilis except for 7-O-succiny1 macrolactin F showing only antibacterial activity.