Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula.
A screening program for bioactive compounds from marine cyanobacteria led to the isolation of jamaicamides A-C. Jamaicamide A is a novel and highly functionalized lipopeptide containing an alkynyl bromide, vinyl chloride, beta-methoxy eneone system, and pyrrolinone ring. The jamaicamides show sodium channelblocking activity and fish toxicity. Precursor feeding to jamaicamide-producing cultures mapped out the series of acetate and amino acid residues and helped develop an effective cloning strategy for the biosynthetic gene cluster. The 58 kbp gene cluster is composed of 17 open reading frames that show an exact colinearity with their expected utilization. A novel cassette of genes appears to form a pendent carbon atom possessing the vinyl chloride functionality; at its core this contains an HMG-CoA synthase-like motif, giving insight into the mechanism by which this functional group is created.
Edwards
Daniel J
DJ
College of Pharmacy, Oregon State University, Corvallis, OR 9733, USA.
Marquez
Brian L
BL
Nogle
Lisa M
LM
McPhail
Kerry
K
Goeger
Douglas E
DE
Roberts
Mary Ann
MA
Gerwick
William H
WH
D000577:Amides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008387:Marine Toxins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D009498:Neurotoxins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011760:Pyrrolidinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
D000577:Amides; D055666:Lipopeptides; D008074:Lipoproteins; D008387:Marine Toxins; D009498:Neurotoxins; D010455:Peptides; D011760:Pyrrolidinones; D015222:Sodium Channels; C494603:jamaicamide A; C494604:jamaicamide B; C494605:jamaicamide C