Biosynthesis and transformation of homoanatoxin-a in the cyanobacterium Raphidiopsis mediterranea Skuja and structures of three new homologues.
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 degrees C) conditions, but the oxidation was prevented in a water solution at both room temperature and -30 degrees 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.
Namikoshi
Michio
M
Department of Ocean Sciences, Tokyo University of Marine Science and Technology, Konan, Minato-ku, Tokyo 108-8477, Japan. namikosh@kaiyodai.ac.jp
Murakami
Tomokazu
T
Fujiwara
Takeshi
T
Nagai
Hiroshi
H
Niki
Takushi
T
Harigaya
Emiko
E
Watanabe
Mariyo F
MF
Oda
Taiko
T
Yamada
Junko
J
Tsujimura
Shigeo
S
D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000458:Cyanobacteria / Q000201:enzymology / Q000378:metabolism*; D008387:Marine Toxins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D040681:Structural Homology, Protein
D001427:Bacterial Toxins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008387:Marine Toxins; C524097:homoanatoxin-a