acetyl-CoA, yielding intermediate 1. This is followed by SxtA-catalyzed methylation of acetyl-ACP, which is then converted to propionyl-ACP, yielding intermediate 2. Later, another SxtA performs a Claisen condensation reaction between propionyl-ACP and arginine producing intermediate 4 and intermediate 3. SxtG transfers an amidino group from an arginine to the α-amino group of intermediate 4 producing intermediate 5. Intermediate 5 then undergoes retroaldol-like condensation by SxtBC, producing intermediate 6. SxtD adds a double bond between C-1 and C-5 of intermediate 6, which gives rise to the 1,2-H shift between C-5 and C-6 in intermediate 7. SxtS performs an epoxidation of the double bond yielding intermediate 8, and then an opening of the epoxide to an aldehyde, forming intermediate 9. SxtU reduces the terminal aldehyde group of the STX intermediate 9, thus forming intermediate 10. SxtIJK catalyzes the transfer of a carbamoyl group to the free hydroxyl group on intermediate 10, forming intermediate 11. SxtH and SxtT, in conjunction with SxtV and the SxtW gene cluster, perform a similar function which is the consecutive hydroxylation of C-12, thus producing saxitoxin and terminating the STX biosynthetic pathway. Illness and poisoning Toxicology Saxitoxin is highly toxic to guinea pigs, fatal at only 5 μg/kg when injected intramuscularly. The lethal doses (LD50) for mice are very similar with varying administration routes: i.v. is 3.4 μg/kg, i.p. is 10 μg/kg and p.o. is 263 μg/kg. The oral LD50 for humans is 5.7 μg/kg, therefore approximately 0.57 mg of saxitoxin (1/8th of a medium-sized grain of sand) is lethal if ingested and the lethal dose by injection is about one-tenth of that (approximately 0.6 μg/kg). The human inhalation toxicity of aerosolized saxitoxin is estimated to be 5 mg·min/m3. Saxitoxin can enter the body via open wounds and a lethal dose of 50 μg/person by this route has been suggested. Illness in humans The human illness associated with ingestion of harmful levels of saxitoxin is known as paralytic shellfish poisoning, or PSP, and saxitoxin and its derivatives are often referred to as "PSP toxins". The medical and environmental importance of saxitoxin derives from the consumption of contaminated shellfish and certain finfish which can concentrate the toxin from dinoflagellates or cyanobacteria. The blocking of neuronal sodium channels which occurs in PSP produces a flaccid paralysis that leaves its victim calm and conscious through the progression of symptoms. Death often occurs from respiratory failure. PSP toxins have been implicated in