Saxitoxin biosynthesis and genomics in organisms from two kingdoms - horizontal gene transfer or parallel evolution?

Paralytic shellfish poisoning is a potentially fatal affliction that results from the consumption of seafood or drinking water, which is infested with the neurotoxic alkaloid saxitoxin and its analogues (PSTs). Although PSTs are produced by a complex and unique biosynthetic pathway, distantly related organisms, which are the cyanobacteria and dinoflagellates, spanning two kingdoms are capable of producing the same toxins by an identical pathway. PSTs are the topic of a considerable number of studies, due to their global impact and pharmacologically valuable properties. Little is known, however, regarding the fundamental biology of these unique metabolites, such as their biosynthesis, metabolic or eco-physiological function, how this pathway has evolved, a nd what its phylogenetic origin is. These questions are addressed in this study. Recently, the gene clusters that are responsible for the biosynthesis of PSTs have been identified from cyanobacteria. This new information will be used as a basis, on which this study will build with the overall goal to comprehensively describe the systems biology of PST-producing microorganisms. Specifically, this study will elucidate the function of each biosynthetic gene in the synthesis of saxitoxin and its analogues, an d the biochemical mechanisms involved. Furthermore, PST-biosynthesis genes will be determined from dinoflagellates to recreate the evolution of these genes with regard to their phylogenetic origin, their relation to other secondary metabolite pathways, an d their possible horizontal gene transfer. This information will shed light on the possible ecological or physiological role of these toxins. The proposed study is expected to make a significant contribution to the field of algal toxin research, both na tionally and internationally.