Polyketides from dinoflagellates: origins, pharmacology and biosynthesis

Dinoflagellates, unicellular marine protists, produce some of the largest a nd most complex polyketides identified to date. The biological activities o f these compounds are quite diverse. Compounds having potential therapeutic value as anti-cancer agents as well as deadly neurotoxins, whose productio n has resulted in severe public health hazards and economic hardships, are represented in this group of secondary metabolites. Stable isotope feeding experiments have firmly established the polyketide origins of representativ e compounds from each of the three structural classes, the polyether ladder s, the macrocycles and the linear polyethers. Yet some unusual labeling pat terns have been observed in each class. Pendant methyl groups are most ofte n derived from C-2 of acetate and deletions of C-1 of acetate are common. S tudies on the biosynthesis of dinoflagellate derived polyketides at the gen omic level have not been reported, in part due to the peculiarities of the dinoflagellate nucleus and the lack of a dinoflagellate transformation syst em. Nevertheless, a fundamental understanding of the genetics of polyketide biosynthesis by dinoflagellates could be the catalyst for developing sever al fruitful avenues of research. Dinoflagellate derived polyketides are rev iewed with special emphasis on pharmacology and biosynthesis. (C) 1999 Else vier Science Inc. All rights reserved.