Multiple Toxin Production in the Cyanobacterium <i>Microcystis</i>: Isolation of the Toxic Protease Inhibitor Cyanopeptolin 1020

Gademann, Karl; Portmann, Cyril; Blom, Judith F.; Zeder, Michael; Jüttner, Friedrich

doi:10.1021/np900818c

Cited by 89 publications

(77 citation statements)

References 30 publications

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“…We could demonstrate that the notorious toxic cyanobacterium Microcystis produces an additional class of toxins, the cyanopeptolins, in addition to the well-known microcystins. [26] Cyanopeptolin 1020 was shown to constitute a 'dirty' protease inhibitor with IC 50 values down to pM concentrations. [26] In addition, we have characterized new microcystin variants both from freshwater strains in Uganda and Austria, and have investigated the structural basis for toxicity.…”

Section: Sb640mentioning

confidence: 99%

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Chemical Interference of Biological Systems with Natural Products

Gademann¹,

Sieber²

2011

Chimia

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Chemical compounds isolated from natural sources offer unique opportunities to understand life on a molecular level. In this account, an overview over different natural products investigated in our research group over the last decade is presented. We have shown that protein localization in living cells can be controlled by anguinomycins and derivatives. Furthermore, a truncated analog, SB640, was discovered that retained much of the natural product potency. Detailed studies of the iron chelator anachelin led to the development of a bio-inspired platform for the generation of bioactive interfaces. The discovery of natural products isolated from cyanobacteria such as nostocarboline, aerucyclamides, cyanopetolin 1020 and various microcystins is presented and their molecular mechanisms of action were investigated. The last part describes the synthesis and evaluation of various natural products involved in neuritogenesis and synapse reconstruction such as withanolide A, militarinone, farinosone A and C and torrubiellone C. Their potential with regard to their use in regenerative medicine is discussed.

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Section: Sb640mentioning

confidence: 99%

“…[26] Cyanopeptolin 1020 was shown to constitute a 'dirty' protease inhibitor with IC 50 values down to pM concentrations. [26] In addition, we have characterized new microcystin variants both from freshwater strains in Uganda and Austria, and have investigated the structural basis for toxicity. [27] Natural Products for Regenerative Medicine…”

Section: Sb640mentioning

confidence: 99%

Chemical Interference of Biological Systems with Natural Products

Gademann¹,

Sieber²

2011

Chimia

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“…However, exposure to these compounds in recreational environments and drinking water may prove to be problematic for ecological and human health since the full effect of cyanobacterial peptides individually, or in mixtures, is still largely unknown. For example, it was recently discovered that cyanopeptolin-1020 displays neurotoxicity in a zebrafish model and inhibits human kallikrein and trypsin in the low pico-to nanomolar range [66,67]. The 50% lethal concentration values against fairy shrimp (Thamnocephalus platyurus) for cyanopeptolin-1020 were similar to that of MCLR .…”

Section: Miscellaneousmentioning

confidence: 96%

Cyanobacterial Toxins of the Laurentian Great Lakes, their Toxicological Effects, and Numerical Limits in Drinking Water

Miller

Beversdorf

Weirich

et al. 2017

Preprint

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Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

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“…We have demonstrated that the structurally unrelated cyanopeptolin 1020 (10) is also a toxin found in Microcystis UV-006. [24] This peptide is a member of the cyanopeptolin class of natural products, featuring a hydroxypiperidone residue as a key structural motif. We have determined very potent inhibitory activity of this peptide against a series of serine proteases, and IC 50 values as low as 670 pM against trypsin have been found.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…We have determined very potent inhibitory activity of this peptide against a series of serine proteases, and IC 50 values as low as 670 pM against trypsin have been found. [24] In addition, a range of other serine proteases such as factor XIa (3.9 nM) and kallikrein (4.5 nM) are strongly inhibited by depsipeptide 10, thus rendering cyanopeptolin 1020 (10) a 'dirty' protease inhibitor. We have also determined a LC 50 value against Thamnocephalus platyurus of 8.8 mM, which is in the same range as some of the well-known microcystins.…”

Section: Acknowledgementsmentioning

confidence: 99%

Out in the Green: Biologically Active Metabolites Produced by Cyanobacteria

Gademann

2011

Chimia

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Dried cyanobacteria ('Spirulina') are sold as a nutraceutical for their high content of proteins, essential fatty acids and vitamins. Beyond spirulina, other genera of cyanobacteria produce interesting small molecules that could find use in nutraceutical or pharmaceutical applications. This account presents recent research efforts on antimalarial nostocarboline and the aerucyclamides, as well as on potent toxins such as cyanopeptolin 1020 and microcystins. Combinations of spectroscopic, computational, chemical and biological studies investigated the mechanism of action of these compounds. Their application potential with regard to nutraceuticals or pharmaceuticals is discussed.

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

Cited by 89 publications

References 30 publications

Chemical Interference of Biological Systems with Natural Products

Chemical Interference of Biological Systems with Natural Products

Cyanobacterial Toxins of the Laurentian Great Lakes, their Toxicological Effects, and Numerical Limits in Drinking Water

Out in the Green: Biologically Active Metabolites Produced by Cyanobacteria

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