Abstract
During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10), were isolated from the extract of a bloom material of Microcystis sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey’s and advance Marfey’s methods and by comparison of 1H and 13C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by N-methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC50) values.
Highlights
Water-bloom forming cyanobacteria are prolific producers of diverse groups of highly active natural products [1]
The relative and absolute configurations of β-amino-α-hydroxy-decanoic (Ahda) or β-amino-α-hydroxy-octanoic acid (Ahoc) in the microginin are of great importance for biological activity [10], and three of the eight possible isomers are known to be produced by cyanobacteria
1–10 were isolated from aqueous-methanol extract of freeze-dried Microcystis sp
Summary
Water-bloom forming cyanobacteria are prolific producers of diverse groups of highly active natural products [1]. (Table S1), and the use of sensitive mass spectroscopy (MS) methods, such as matrix-assisted laser desorption/ionization (MALDI) MS/MS and electrospray ionization (ESI) MS/MS, for the characterization of secondary metabolites of cyanobacterial bloom materials has enabled identified at least fifteen additional sequences of peptides belonging to the microginin group of metabolites [11,12]. These most recently identified microginins have been partially characterized with respect to their activities, the absolute configurations of the chiral centers of the amino acids, and the identities of N-methylated amino acids and aliphatic amino acids (i.e., NMe-valine versus leucine and isoleucine). The relative and absolute configurations of β-amino-α-hydroxy-decanoic (Ahda) or β-amino-α-hydroxy-octanoic acid (Ahoc) in the microginin are of great importance for biological activity [10], and three of the eight possible isomers are known to be produced by cyanobacteria
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