Balticidins A-D, antifungal hassallidin-like lipopeptides from the Baltic Sea cyanobacterium Anabaena cylindrica Bio33.

Abstract

Balticidins A-D (1-4), four new antifungal lipopeptides, were isolated from the laboratory-cultivated cyanobacterium Anabaena cylindrica strain Bio33 isolated from a water sample collected from the Baltic Sea, Rügen Island, Germany. Fractionation of the 50% aqueous MeOH extract was performed by bioassay-guided silica gel column chromatography followed by SPE and repeated reversed-phase HPLC. The main fraction containing the compounds exhibited a strong and specific antifungal activity with inhibition zones in an agar-diffusion assay from 21 to 32 mm against Candida albicans, Candida krusei, Candida maltosa, Aspergillus fumigatus, Microsporum gypseum, Mucor sp., and Microsporum canis. The structures were elucidated by multidimensional (1)H and (13)C NMR spectroscopy, HRESIMS, amino acid analysis, and sugar analysis. Spectroscopic data analysis afforded an unambiguous sequence of R.CHO(S1).CHOH.CONH-Thr(1)-Thr(2)-Thr(3)-HOTyr(4)-Dhb(5)-D-Gln(6)-Gly(7)-NMeThr(8)(S2)-L-Gln COOH(9), in which Dhb is dehydroaminobutyric acid, S1 is d(-)-arabinose-(3-1)-D-(+)-galacturonic acid, S2 is D-(+)-mannose, and R is the aliphatic residue -C13H26Cl or -C13H27. Besides NMeThr, D-allo-Thr, D-Thr, and L-Thr were identified, but the position of the enantiomers in the sequence is not clear. The four balticidins differ in their cyclic (2, 4)/linear (1, 3) core and the presence (1, 2)/absence (3, 4) of chlorine in the aliphatic unit.