Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152.
Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1), [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3), were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152, together with four known microcystins, [ADMAdda5]microcystin-LR (4), [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS), collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas chromatography (GC) on a chiral capillary column. All three new toxins contained 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda) instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit which was thought to be an invariable amino acid component of the microcystins. Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D-aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in 5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine unit in 4, would be a biosynthetic precursor of 4.
Sivonen
K
K
Department of Microbiology, University of Helsinki, Finland.
Namikoshi
M
M
Evans
W R
WR
Färdig
M
M
Carmichael
W W
WW
Rinehart
K L
KL
D000596:Amino Acids / Q000032:analysis; D001427:Bacterial Toxins / Q000737:chemistry* / Q000302:isolation & purification; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D000458:Cyanobacteria / Q000737:chemistry*; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects*; D052998:Microcystins; D015394:Molecular Structure; D008970:Molecular Weight; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000596:Amino Acids; D001427:Bacterial Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C077084:(SER(1)-ADMADDA(5))MICROSYSTIN-LR; C077086:(ADMAAdda(5)-MSer(7))microsystin-LR; C077085:(Asp(3)-ADMAAdda(5))microcystin-LHar