Halovirs I-K, antibacterial and cytotoxic lipopeptaibols from the plant pathogenic fungus Paramyrothecium roridum NRRL 2183.

Abstract

Three new lipopeptaibols, halovirs I-K (1-3), were isolated from the solid culture of the phytopathogenic fungus Paramyrothecium roridum NRRL 2183. Their planar structures, which consist of a hexapeptide backbone and acyl substitutions at the N- and C-termini, were elucidated by comprehensive analysis of the 1D and 2D NMR spectroscopic data along with the detailed interpretation of the MS/MS fragmentation pattern. Absolute configurations of the amino acid/1,2-amino alcohol residues were determined using the advanced Marfey's method. Bioinformatics analysis of the genome assembly of P. roridum NRRL 2183 revealed a gene cluster that is likely responsible for the biosynthesis of halovirs I-K. Analysis of the module and domain organization of the putative halovir synthetase PrHalA indicated that the assembly of 1-3 proceeds in an unconventional nonlinear fashion. 1 and 2 exhibited potent antibacterial activity against both antibiotic-sensitive and multidrug-resistant Gram-positive pathogens. These lipopeptaibols also displayed significant cytotoxicity toward human lung carcinoma A549, human breast carcinoma MCF-7, and human cervical carcinoma HeLa cells with IC50 values ranging from 1.3 to 3.3 μM.