Nostophycin, a novel cyclic peptide from the toxic cyanobacterium Nostoc sp 152

For the elucidation of the biosynthetic relationship between nontoxic and hepatotoxic peptides produced by cyanobacteria, we investigated the secondary metabolites from the toxic cyanobacterium Nostoc sp. strain 152, which produces microcystins. A novel cyclic peptide, nostophycin, possessing weakly cytotoxic activity was isolated together with microcystins from this strain. Nostophycin is composed of six amino acids, D-glutamine, glycine, L-phenylalanine, D-allo-isoleucine, 2 mol of L-proline, and a novel beta-amino acid moiety, (2S,3R,5R)-3-amino-2,5-dihydroxy-8-phenyloctanoic acid (Ahoa). The sequence of the constituent amino acids in nostophycin and its structure were determined by 2D-NMR techniques and MS/MS experiments, and the advanced Marfey's method has been used to simultaneously determine their absolute configurations including the beta-amino acid moiety. The stereochemistries at the C-2 and C-5 positions of Ahoa were determined by the H-1 NMR spectral analysis of its lactone derivative with the acetylation. These results suggest that nostophycin is biosynthetically related to the microcystins, because they have a beta-amino acid and two D-amino acids in common.