Simultaneous production of homoanatoxin-a, anatoxin-a, and a new non-toxic 4-hydroxyhomoanatoxin-a by the cyanobacterium Raphidiopsis mediterranea Skuja

Michio Namikoshi, Tomokazu Murakami, Mariyo F. Watanabe, Taiko Oda, Junko Yamada, Shigeo Tsujimura, Hiroshi Nagai, Shinshi Oishi

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

A neurotoxin, homoanatoxin-a, was identified from a toxic strain of the cyanobacterium Raphidiopsis mediterranea Skuja (strain LBRI 48) isolated from Lake Biwa, Japan, as the major toxin component (0.57% of dry cell-weight). This cyanobacterium produced anatoxin-a and a new homoanatoxin-a derivative as minor components (0.04 and 0.06%, respectively). The structure of a new compound was assigned based on the spectral data as 4-hydroxyhomoanatoxin-a, which was not toxic to mice up to 2.0 mg/kg by intraperitoneal injection. The isolation of minor components was accomplished by improved extraction and separation procedures: (1) extraction with methanol-water (4:1) from dried cells, (2) adsorption of aqueous residue on ODS column (or cartridge) after evaporation of methanol, (3) cleaning up of the column by successive elution with water and 50% methanol/water, (4) elution of a toxic fraction by 20% methanol/water containing 0.1% TFA and (5) HPLC (ODS) purification with methanol/water containing 0.05% TFA. The procedures were effective in removing impurities and concentrating alkaloidal neurotoxins. It should be noted that this is the first report demonstrating the simultaneous production of anatoxin-a and homoanatoxin-a by the same strain of cyanobacterium.

Original languageEnglish
Pages (from-to)533-538
Number of pages6
JournalToxicon
Volume42
Issue number5
DOIs
Publication statusPublished - 2003 Oct

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Cyanobacteria
Methanol
Poisons
Water
Neurotoxins
Distillation columns
Lakes
Intraperitoneal Injections
Adsorption
Purification
Cleaning
Japan
Evaporation
High Pressure Liquid Chromatography
Cells
anatoxin a
4-hydroxyhomoanatoxin-a
homoanatoxin-a
Impurities
Derivatives

Keywords

  • 4-Hydroxyhomoanatoxin-a
  • Anatoxin-a
  • Cyanobacterium
  • Homoanatoxin-a
  • Neurotoxin
  • Raphidiopsis mediterranea

ASJC Scopus subject areas

  • Toxicology

Cite this

Simultaneous production of homoanatoxin-a, anatoxin-a, and a new non-toxic 4-hydroxyhomoanatoxin-a by the cyanobacterium Raphidiopsis mediterranea Skuja. / Namikoshi, Michio; Murakami, Tomokazu; Watanabe, Mariyo F.; Oda, Taiko; Yamada, Junko; Tsujimura, Shigeo; Nagai, Hiroshi; Oishi, Shinshi.

In: Toxicon, Vol. 42, No. 5, 10.2003, p. 533-538.

Research output: Contribution to journalArticle

Namikoshi, Michio ; Murakami, Tomokazu ; Watanabe, Mariyo F. ; Oda, Taiko ; Yamada, Junko ; Tsujimura, Shigeo ; Nagai, Hiroshi ; Oishi, Shinshi. / Simultaneous production of homoanatoxin-a, anatoxin-a, and a new non-toxic 4-hydroxyhomoanatoxin-a by the cyanobacterium Raphidiopsis mediterranea Skuja. In: Toxicon. 2003 ; Vol. 42, No. 5. pp. 533-538.
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AU - Oda, Taiko

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AB - A neurotoxin, homoanatoxin-a, was identified from a toxic strain of the cyanobacterium Raphidiopsis mediterranea Skuja (strain LBRI 48) isolated from Lake Biwa, Japan, as the major toxin component (0.57% of dry cell-weight). This cyanobacterium produced anatoxin-a and a new homoanatoxin-a derivative as minor components (0.04 and 0.06%, respectively). The structure of a new compound was assigned based on the spectral data as 4-hydroxyhomoanatoxin-a, which was not toxic to mice up to 2.0 mg/kg by intraperitoneal injection. The isolation of minor components was accomplished by improved extraction and separation procedures: (1) extraction with methanol-water (4:1) from dried cells, (2) adsorption of aqueous residue on ODS column (or cartridge) after evaporation of methanol, (3) cleaning up of the column by successive elution with water and 50% methanol/water, (4) elution of a toxic fraction by 20% methanol/water containing 0.1% TFA and (5) HPLC (ODS) purification with methanol/water containing 0.05% TFA. The procedures were effective in removing impurities and concentrating alkaloidal neurotoxins. It should be noted that this is the first report demonstrating the simultaneous production of anatoxin-a and homoanatoxin-a by the same strain of cyanobacterium.

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