is a neurotoxin that acts as a selective, reversible, voltage-gated sodium channel blocker. One of the most potent known natural toxins, it acts on the voltage-gated sodium channels of neurons, preventing normal cellular function and leading to paralysis. The voltage-gated sodium channel is essential for normal neuronal functioning. It exists as integral membrane proteins interspersed along the axon of a neuron and possessing four domains that span the cell membrane. Opening of the voltage-gated sodium channel occurs when there is a change in voltage or some ligand binds in the right way. It is of foremost importance for these sodium channels to function properly, as they are essential for the propagation of an action potential. Without this ability, the nerve cell becomes unable to transmit signals and the region of the body that it enervates is cut off from the nervous system. This may lead to paralysis of the affected region, as in the case of saxitoxin. Saxitoxin binds reversibly to the sodium channel. It binds directly in the pore of the channel protein, occluding the opening, and preventing the flow of sodium ions through the membrane. This leads to the nervous shutdown described above. Biosynthesis Although the biosynthesis of saxitoxin seems complex, organisms from two different kingdoms, indeed two different domains, species of marine dinoflagellates and freshwater cyanobacteria, are capable of producing these toxins. While the prevailing theory of production in dinoflagellates was through symbiotic mutualism with cyanobacteria, evidence has emerged suggesting that dinoflagellates, themselves, also possess the genes required for saxitoxin synthesis. Saxitoxin biosynthesis is the first non-terpene alkaloid pathway described for bacteria, though the exact mechanism of saxitoxin biosynthesis is still essentially a theoretical model. The precise mechanism of how substrates bind to enzymes is still unknown, and genes involved in the biosynthesis of saxitoxin are either putative or have only recently been identified. Two biosyntheses have been proposed in the past. Earlier versions differ from a more recent proposal by Kellmann, et al. based on both biosynthetic considerations as well as genetic evidence not available at the time of the first proposal. The more recent model describes a STX gene cluster (sxt) used to obtain a more favorable reaction. The most recent reaction sequence of Sxt in cyanobacteria is as follows. Refer to the diagram for a detailed biosynthesis and intermediate structures. It begins with the loading of the acyl carrier protein (ACP) with acetate from