Isolation of linear peptides related to the hepatotoxins nodularin and microcystins

Linear peptide 2, Adda-D-Glu(γ)-Mdhb-D-MeAsp(β)-L-Arg-OH, was isolated from cultured Nodularia spumigena and was analyzed in the cells after one week's (1:2 : 30:1) to eight week's (>100:1) cultivation. Three linear peptides, Adda-D-Glu(γ)-Mdha-D-Ala-L-Leu-D-MeAsp(β)-L-Arg-OH (3), L-Leu-D-MeAsp(β)-L-Arg-Adda-D-Glu(γ)-Mdha-D-Ala-OH (4), and L-Phe-D-MeAsp(β)-L-Arg-Adda-D-Glu(γ)-Mdha-D-Ala-OH (5) were obtained from a water bloom of Microcystis spp. collected from Homer Lake (Illinois). Some of these linear peptides (2,3) are thought to be biogenetic precursors of nodularin and microcystins. Linear peptides 2, 3, and 4 did not show apparent toxicity at 1.0, 1.1, and 2.25 mg/kg, respectively, in a mouse bioassay (ip). Feeding experiments using ¹³C-labeled precursors established that the 2-, 6- and 8-methyl and 9-methoxy carbons of the unusual (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda) unit of 1 were clearly derived from L-methionine.