Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum

Wagoner, Ryan M. Van; Deeds, Jonathan R.; Satake, Masayuki; Ribeiro, Anthony A.; Place, Allen R.; Wright, Jeffrey L. C.

doi:10.1016/j.tetlet.2008.08.103

Cited by 97 publications

(87 citation statements)

References 31 publications

(43 reference statements)

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“…amphidinols with hairpin structures, are believed to interact with sterols located in the membrane, and to increase the membrane permeability by forming pores in the membrane (Houdai et al, 2005). Karlotoxins (KmTxs) are another group of toxic dinoflagellate metabolites, with structures similar to amphidinols (Van Wagoner et al, 2008). KmTx-2 exhibited different affinities to gymnodinosterol, a 4-methyl sterol from Karlodinium veneficum, cholesterol (found in erythrocytes as well as O. marina), and ergosterol, a fungal sterol (Deeds and Place, 2006).…”

Section: Discussionmentioning

confidence: 99%

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Krock

Tillmann

et al. 2011

Toxicon

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a b s t r a c tCertain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause lysis of a broad spectrum of target protist cells but the lytic mechanism is poorly defined. We first hypothesized that membrane sterols serve as molecular targets of these lytic compounds, and that differences in sterol composition among donor and target cells may cause insensitivity of Alexandrium and sensitivity of targets to lytic compounds. We investigated Ca 2þ influx after application of lytic fractions to a model cell line PC12 derived from a pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds affect ion flux associated with lysis of target membranes. The lytic compounds increased permeability of the cell membrane for Ca 2þ ions even during blockade of Ca 2þ channels with cadmium. Results of a liposome assay suggested that the lytic compounds did not lyse such target membranes non-specifically by means of detergent-like activity. Analysis of sterol composition of isolates of A. tamarense and of five target protistan species showed that both lytic and non-lytic A. tamarense strains contain cholesterol and dinosterol as major sterols, whereas none of the other tested species contain dinosterol. Adding sterols and phosphatidylcholine to a lysis bioassay with the cryptophyte Rhodomonas salina for evaluation of competitive binding indicated that the lytic compounds possessed apparent high affinity for free sterols and phosphatidylcholine. Lysis of protistan target cells was dose-dependently reduced by adding various sterols or phosphatidylcholine. For three tested sterols, the lytic compounds showed highest affinity towards cholesterol followed by ergosterol and brassicasterol. Cholesterol comprised a higher percentage of total sterols in plasma membrane fractions of A. tamarense than in corresponding whole cell fractions. We conclude therefore that although the molecular targets of the lytic compounds are likely to involve sterol components of membranes, A. tamarense must have a complex selfprotective mechanism that still needs to be addressed.

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Section: Discussionmentioning

confidence: 99%

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Krock

Tillmann

et al. 2011

Toxicon

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“…Karlodinium veneficum is one such dinoflagellate. It is a producer of karlotoxins (KmTxs), a group of toxins with hemolytic, cytotoxic and ichthyotoxic activities [3][4][5]. KmTxs are a potential basis for design of drugs for treatment of heart disease and some cancers [6].…”

Section: Introductionmentioning

confidence: 99%

An optimal culture medium for growing Karlodinium veneficum : Progress towards a microalgal dinoflagellate-based bioprocess

et al. 2015

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“…The only exception is maitotoxin with a molecular mass of 3422 g mol -1 , the largest non-biopolymer natural product known (Murata et al, 1994). Karlotoxins from the dinoflagellate Karlodinium veneficum (Bachvaroff et al, 2008;Van Wagoner et al, 2008) as well as amphidinols from Amphidium klebsii (Houdai et al, 2004;Houdai et al, 2005) have a similar mass range of about 1300 Da and membrane disruptive properties. These compounds form hairpin structures suggested to be important for the interaction with lipid bilayers of biomembranes.…”

Section: Unique Masses Found In Spe Fractionsmentioning

confidence: 99%

Isolation of activity and partial characterization of large non-proteinaceous lytic allelochemicals produced by the marine dinoflagellate Alexandrium tamarense

Krock

Tillmann

et al. 2011

Harmful Algae

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Certain strains of the toxigenic dinoflagellate Alexandrium tamarense produce potent allelochemicals with lytic activity against a wide variety of marine microorganisms. Our efforts to characterize these allelochemicals from a lytic strain focused on the less polar components because of their higher lytic activity.Fractionation and partial purification after solid phase extraction (SPE) were achieved via alternative chromatographic methods, namely HPLC separation on C8 and HILIC phases. Through MALDI-TOF mass spectrometry we compared the mass differences in SPE, C8 HPLC, and HILIC fractions between a lytic and non-lytic strain of A.tamarense. Several large species with masses between 7 kDa and 15 kDa were found in the HILIC lytic fraction by MALDI-TOF MS. Tryptic digestion and tryptic digestion-coupled size-exclusion chromatography (SEC) suggested that the lytic compounds are large non-proteinaceous molecules (<23.3 kDa, trypsin). Although there is no direct proof that the large molecules found in the lytic HILIC fraction are responsible for the lytic activity of this fraction, the mass range deduced from SEC strongly supports this hypothesis. Total sugar content analysis showed that the lytic HILIC fraction contained two-fold more sugar than the non-lytic one. Nevertheless, the low percentage of saccharide per dry mass equivalent (0.18 ± 0.01 %) indicates that sugar residues are likely not a major component of the lytic compounds. We concluded that at least one group of lytic allelochemicals produced by A. tamarense comprise a suite of large non-proteinaceous and probably non-polysaccharide compounds between 7 kDa and 15 kDa.

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Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum

Cited by 97 publications

References 31 publications

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

An optimal culture medium for growing Karlodinium veneficum : Progress towards a microalgal dinoflagellate-based bioprocess

Isolation of activity and partial characterization of large non-proteinaceous lytic allelochemicals produced by the marine dinoflagellate Alexandrium tamarense

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