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.

Coibamide A (1) is a new, potent antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium collected from the Coiba National Park, Panama. The planar structure of 1 was elucidated by a combination of NMR spectroscopy and mass spectrometry. Exhaustive 1D and 2D NMR spectroscopy included natural abundance 15 N and variable temperature experiments; mass spectrometry included TOF-ESI-MS n and FT-MS n experiments. Chemical degradation followed by chiral HPLC-and GC-MS analyses was used to assign the absolute configuration of 1. This highly methylated cyclized depsipeptide exhibited an unprecedented selectivity profile in the NCI 60 cancer cell line panel and appears to act via a novel mechanism.Marine organisms continue to yield a diverse array of biologically active molecules, a remarkable number of which are peptide-based cancer cell toxins of putative microbial symbiont biogenesis. 1 Development of these as anticancer drugs has met with some success: 2 ascidian-derived dihydrodidemnin B (aplidin®) has orphan drug status for the treatment of multiple myeloma and acute lymphoblastic leukemia; green algal isolate kahalalide F, and TZT-1027, a synthetic analog of the cyanobacterial metabolite dolastatin 10, reached phase II clinical trials. Other important cyanobacterial peptide leads include the cryptophycins and curacin A, 3 and these organisms continue to produce a wealth of anticancer lead compounds. 4 The high degree of N-methylation of many of these cyanobacterial peptides may improve their druggability since N-methylation has been shown to improve pharmacological parameters such as lipophilicity, proteolytic stability and duration of action, properties for which regular peptides are notoriously poor and which limits their bioavailability. 5In the context of our International Cooperative Biodiversity Groups program (ICBG) based in Panama, which focuses on drug discovery, biodiversity conservation and sustainable economic growth, we have isolated a potent cancer cell toxin with an unprecedented selectivity profile in the NCI 60 cell line panel. This cyanobacterial depsipeptide, named coibamide A in tribute

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