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

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.

Recent Advances in Exploration and Biotechnological Production of Bioactive Compounds in Three Cyanobacterial Genera: Nostoc, Lyngbya, and Microcystis

“…The micropeptins KB992 and KB1046 also inhibited chymotrypsin in a similar range of IC 50 (Elkobi-Peer and Carmeli, 2015). Likewise, it was reported that micropeptin TR1058 inhibited chymotrypsin with an IC 50 6.78 μM (Hasan-Amer and Carmeli, 2017).…”

“…Different structures belonging to micropeptins, such as KB928, KB956, KB970A, KB970B, KB984, KB970C, KB1048, KB992, KB1046, TR1058, KR1030, KR1002, KR998, MZ845, MZ859, MZ939A, MZ925, MZ939B, MZ1019, MZ771, LH920, LH1021, LH1048, LH1062, LH911A, LH911B, LH911C, and LH925 were isolated from a Microcystis collected in diverse water reservoirs (fishpond, secondary water pond, etc.,) (Zafrir and Carmeli, 2010; Bladt et al, 2014; Elkobi-Peer and Carmeli, 2015; Hasan-Amer and Carmeli, 2017).…”

“…Aeruginosins DA495A, DA511, DA642A, DA642B, DA688, DA722, DA495B, LH650A, LH650B, LH606, KB676, and TR642 were isolated in various locations in Israel (Adiv and Carmeli, 2013; Vegman and Carmeli, 2014; Elkobi-Peer and Carmeli, 2015; Hasan-Amer and Carmeli, 2017).…”

“…Aeruginosins LH650A, LH650B, and LH606 showed mild inhibition against trypsin whereas higher inhibition against thrombin (Vegman and Carmeli, 2014). Aeruginosin KB676 inhibited trypsin with sub-μM IC 50 but aeruginosin TR642 inhibited trypsin and thrombin (Elkobi-Peer and Carmeli, 2015; Hasan-Amer and Carmeli, 2017).…”

Isolation and Structure Elucidation of Secondary Metabolites from a Microcystis sp. Bloom Material Collected in Southern Israel

“…The aeruginosins, with at least 81 members [12], are second to the micropeptins, in the number of analogs. The aeruginosins are linear peptides composed of three or four building blocks, a hydroxyl acid or a fatty acid at the N-terminus, a lipophilic amino acid at the second position, 2-carboxy-6-hydroxyoctahydroindole (Choi) or proline at the third position, and, if present, an arginine derivative at the fourth position [7].…”