Inhibitors of Serine Proteases from a Microcystis sp. Bloom Material Collected from Timurim Reservoir, Israel.

Rawan Hasan-Amer,Shmuel Carmeli

doi:10.3390/md15120371

Abstract

Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation conditions, and several degradation products were identified. NMR analysis of aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal subunit that has not been described before. Micropeptin TR1058 (1) inhibited chymotrypsin with an IC50 of 6.78 µM, and aeruginosin TR642 (2) inhibited trypsin and thrombin with inhibition concentration (IC50) values of 3.80 and 0.85 µM, respectively. The structures and biological activities of the new compounds are discussed.

Highlights

Water bloom-forming genera of cyanobacteria, including Microcystis, produce biologically active natural products including toxins such as the microcystins, protease inhibitors such as the micropeptins, aeruginosins, anabaenopeptins, microginins, microviridins, and other biologically active natural products [1]
Microcystis blooms usually contain various species or chemotypes that produce a large variety of short peptides; the micropeptins are dominant in quantity and diversity [10]
The toxic microcystins are second in diversity and are usually present in minute quantities relative to the micropeptins [2]

Summary

Introduction

Water bloom-forming genera of cyanobacteria, including Microcystis, produce biologically active natural products including toxins such as the microcystins, protease inhibitors such as the micropeptins, aeruginosins, anabaenopeptins, microginins, microviridins, and other biologically active natural products [1]. The microcystins are a group of more than 100 cyclic heptapeptides that are biosynthesized by non-ribosomal peptide synthetase. 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadieneoic acid (Adda), iso-linked glutamic acid, NMe-dehydro-alanine (Mdha) or -aminobutyric acid (Mdhb), D-alanine, a variable L-amino acid, iso-linked D-aspartic or methylaspartic acid, and a variable L-amino acid links to the amine of. The microcystins are the best characterized of cyanobacterial metabolites. These natural products have been studied for their toxicity, tumor promotion, biosynthesis [2], chemical diversity [3], and environmental impact [4].

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Results

Conclusion