Cyanopeptolin SS, a disulphated depsipeptide from a water bloom: structural elucidation and biological activities

Jakobi, Clemens; Rinehart, Kenneth L.; Neuber, Rolf; Mez, Konstanze; Weckesser, Jürgen

doi:10.2216/i0031-8884-35-6s-111.1

Cited by 41 publications

(33 citation statements)

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“…However, this cyanobacterium has been shown to inhibit chymotrypsins (Schwarzenberger et al, 2013), and actually three different chymotrypsin inhibitors were identified in our study: micropeptin DR1056, micropeptin DR1006 and micropeptin MM978. Such protease inhibitors have been found in many blooms worldwide (Jakobi et al, 1996;Jakobi et al, 1995;Agrawal et al, 2001;Czarnecki et al, 2006), suggesting that they are among the most frequent cyanobacterial secondary metabolites. Only recently has the seasonal succession of chymotrypsin inhibition been studied .…”

Section: Discussionmentioning

confidence: 99%

“…These protease inhibitors have been found in many cyanobacterial blooms (Jakobi et al, 1996;Jakobi et al, 1995;Agrawal et al, 2001;Czarnecki et al, 2006; and have been shown to inhibit digestive serine proteases of D. magna both in vitro (Agrawal et al, 2005) and in situ (Schwarzenberger et al, 2010). These serine proteases represent the most important digestive enzymes in the gut of D. magna (Von Elert et al, 2004).…”

Section: Introductionmentioning

confidence: 98%

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Effect of nutrient limitation of cyanobacteria on protease inhibitor production and fitness ofDaphnia magna

Schwarzenberger

Sadler

Elert

2013

Journal of Experimental Biology

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SUMMARYHerbivore-plant interactions have been well studied in both terrestrial and aquatic ecosystems as they are crucial for the trophic transfer of energy and matter. In nutrient-rich freshwater ecosystems, the interaction between primary producers and herbivores is to a large extent represented by Daphnia and cyanobacteria. The occurrence of cyanobacterial blooms in lakes and ponds has, at least partly, been attributed to cyanotoxins, which negatively affect the major grazer of planktonic cyanobacteria, i.e. Daphnia. Among these cyanotoxins are the widespread protease inhibitors. These inhibitors have been shown (both in vitro and in situ) to inhibit the most important group of digestive proteases in the gut of Daphnia, i.e. trypsins and chymotrypsins, and to reduce Daphnia growth. In this study we grew cultures of the cyanobacterium Microcystis sp. strain BM25 on nutrient-replete, N-depleted or P-depleted medium. We identified three different micropeptins to be the cause for the inhibitory activity of BM25 against chymotrypsins. The micropeptin content depended on nutrient availability: whereas N limitation led to a lower concentration of micropeptins per biomass, P limitation resulted in a higher production of these chymotrypsin inhibitors. The altered micropeptin content of BM25 was accompanied by changed effects on the fitness of Daphnia magna: a higher content of micropeptins led to lower IC 50 values for D. magna gut proteases and vice versa. Following expectations, the lower micropeptin content in the Ndepleted BM25 caused higher somatic growth of D. magna. Therefore, protease inhibitors can be regarded as a nutrientdependent defence against grazers. Interestingly, although the P limitation of the cyanobacterium led to a higher micropeptin content, high growth of D. magna was observed when they were fed with P-depleted BM25. This might be due to reduced digestibility of P-depleted cells with putatively thick mucilaginous sheaths. These findings indicate that both the grazer and the cyanobacterium benefit from P reduction in terms of digestibility and growth inhibition, which is an interesting starting point for further studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Effect of nutrient limitation of cyanobacteria on protease inhibitor production and fitness ofDaphnia magna

Schwarzenberger

Sadler

Elert

2013

Journal of Experimental Biology

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“…Microcystilide A when applied intraperitoneally to mice induced convulsions and spasms but not death. 5 Cyanopeptolin SS isolated from a natural cyanobacterial bloom caused death of crustaceans 6 as did oscillapeptin J for Thamnocephalus platyurus. 7 While little is known about the toxicity of cyanopeptolins, the most studied cyanobacterial toxins are the microcystins, which exert their hepatotoxicity through protein phosphatase inhibition 8 and are produced by species of the genera Microcystis, Anabaena, Oscillatoria, Planktothrix, and Nostoc.…”

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confidence: 99%

Multiple Toxin Production in the Cyanobacterium Microcystis: Isolation of the Toxic Protease Inhibitor Cyanopeptolin 1020

et al. 2010

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The isolation and structure of cyanopeptolin 1020 (hexanoic acid-Glu-N[-O-Thr-Arg-Ahp-Phe-N-Me-Tyr-Val-]) from a Microcystis strain is reported. Very potent picomolar trypsin inhibition (IC50 = 670 pM) and low nanomolar values against human kallikrein (4.5 nM) and factor XIa (3.9 nM) have been determined for cyanopeptolin 1020. For plasmin and chymotrypsin, low micromolar concentrations were necessary for 50% inhibition. Cyanopeptolin 1020 was found to be toxic against the freshwater crustacean Thamnocephalus platyurus (LC50 = 8.8 μM), which is in the same range as some of the well-known microcystins. These data support the hypothesis that cyanopeptolins can be considered as a second class of toxins in addition to the well-established microcystins in Microcystis.

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“…Evidence suggests that they inhibit trypsin-like enzymes in Daphnia and thus may target the digestion process in zooplankton (Agrawal et al 2005;Czarnecki et al 2006). In fact, the trypsin-inhibitory peptides cyanopeptolin SS (Jakobi et al 1996), microviridin J (Rohrlack et al 2003) and oscillapeptin J (Blom et al 2003) are reported to be toxic to Daphnia. Studies also suggest a role of microcystins and the other peptides in allelopathic interactions, siderophoric scavenging of iron, gene expression and quorum sensing (Dittmann et al 2001;Babica et al 2006;Martin-Luna et al 2006;Schatz et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Proteolytic activity in Microcystis aeruginosa PCC7806 is inhibited by a trypsin-inhibitory cyanobacterial peptide with a partial structure of microviridin

Ghosh

Bagchi

2008

J Appl Phycol

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This paper describes the characterization of proteases in Microcystis aeruginosa PCC7806 cells being inhibited by a metabolite produced by another Microcystis strain, Microcystis Ku1. With casein and oligopeptide substrates and specific inhibitors we detected activity similar to bacterial serine endoproteases. Substrate SDSpolyacrylamide gel electrophoresis revealed the presence of nine bands of proteases (ca. 35∼125 kDa). The cyanobacterial enzymes were insensitive to endogenous trypsin-inhibitory metabolites. Microcystis Ku1 produced a metabolite, tentatively characterized as microviridin, inhibiting both cyanobacterial proteases and trypsin at an estimated IC 50 of, respectively, 2.2 and 9.0 μg mL −1 . On activity gels, inhibitors specific to animal trypsin and elastase and the putative microviridin led to an inactivation of the proteases associated with the 88 and 110 kDa bands. We hypothesize that in Microcystis populations there is a "cross-talk" between the inhibitors and the proteases, and only the colonies of identical chemotypes can possibly aggregate to form blooms.

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Cyanopeptolin SS, a disulphated depsipeptide from a water bloom: structural elucidation and biological activities

Cited by 41 publications

References 0 publications

Effect of nutrient limitation of cyanobacteria on protease inhibitor production and fitness ofDaphnia magna

Effect of nutrient limitation of cyanobacteria on protease inhibitor production and fitness ofDaphnia magna

Multiple Toxin Production in the Cyanobacterium Microcystis: Isolation of the Toxic Protease Inhibitor Cyanopeptolin 1020

Proteolytic activity in Microcystis aeruginosa PCC7806 is inhibited by a trypsin-inhibitory cyanobacterial peptide with a partial structure of microviridin

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