C–H Hydroxylation in Paralytic Shellfish Toxin Biosynthesis

摘要: The remarkable degree of synthetic selectivity found in Nature is exemplified by the biosynthesis paralytic shellfish toxins such as saxitoxin. polycyclic core shared saxitoxin and its relatives assembled subsequently elaborated through installation hydroxyl groups with exquisite precision that not possible to replicate traditional methods. Here, we report identification enzymes carry out a subset C-H functionalizations involved toxin biosynthesis. We have shown three Rieske oxygenases mediate hydroxylation reactions perfect site- stereoselectivity. Specifically, oxygenase SxtT responsible for selective tricyclic precursor famous natural product saxitoxin, second oxygenase, GxtA, selectively hydroxylates access oxidation pattern present gonyautoxin products. Unexpectedly, third SxtH, does hydroxylate intermediates, but rather linear substrate prior tricycle formation, rewriting biosynthetic route toxins. Characterization SxtT, GxtA first demonstration carrying Additionally, these suite saxitoxin-related molecules are reported, highlighting promiscuity catalysts potential their application synthesis unnatural congeners.