Biosynthesis and transformation of homoanatoxin-a in the cyanobacterium Raphidiopsis mediterranea skuja and structures of three new homologues

Michio Namikoshi, Tomokazu Murakami, Takeshi Fujiwara, Hiroshi Nagai, Takushi Niki, Emiko Harigaya, Mariyo F. Watanabe, Taiko Oda, Junko Yamada, Shigeo Tsujimura

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Abstract

The biosynthetic origin of the C-12 methyl group in homoanatoxin-a (1) was identified by the feeding experiment of L-[methyl-13C]-methionine in the culture of the cyanobacterium Raphidiopsis mediterranea Skuja strain LBRI 48. Remarkably high incorporation (80%) of 13C was observed at C-12. The in vivo enzymatic transformation of 1 was also examined by the prolonged culture of strain LBRI 48. The cells harvested at the stationary phase (15 days of incubation) gave higher contents of 4S-hydroxyhomoanatoxin-a (2), 4R-hydroxyhomoanatoxin-a (3), 2,3-epoxyhomoanatoxin-a (4), and 4-ketohomoanatoxin-a (5) than those from the cells collected at the late logarithmic growth phase (5 days). Compounds 2-5 would be transformed from 1 in the cells. The ratio of anatoxin-a and 1 was not significantly changed between two phases. Compound 5 was generated from 1 by air oxidation during storage even under dry and cool (-30 °C) conditions, but the oxidation was prevented in a water solution at both room temperature and -30 °C (frozen stock). Homoanatoxin-a (1) gave 2,3-dihydro-3-methoxyhomoanatoxin-a (6) during the separation procedures probably by the Michael reaction of methanol used as solvent. It should be noted that 4 was isolated for the first time from a cyanobacterium as the natural product. Compounds 3 and 5 were new members of the anatoxins.

Original languageEnglish
Pages (from-to)1692-1696
Number of pages5
JournalChemical Research in Toxicology
Volume17
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1

ASJC Scopus subject areas

  • Toxicology

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    Namikoshi, M., Murakami, T., Fujiwara, T., Nagai, H., Niki, T., Harigaya, E., Watanabe, M. F., Oda, T., Yamada, J., & Tsujimura, S. (2004). Biosynthesis and transformation of homoanatoxin-a in the cyanobacterium Raphidiopsis mediterranea skuja and structures of three new homologues. Chemical Research in Toxicology, 17(12), 1692-1696. https://doi.org/10.1021/tx0498152