The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many secondary aromatic metabolites. The shikimate pathway is essential for most bacteria and plants but absent in animals.The dehydration of dehydroquinate to dehydroshikimate is an essential step in the shikimate pathway and is thus an attractive target for the development of novel antibiotics. In the pharmaceutical industry, shikimic acid from the Chinese star anise is used as a base material for production of Tamiflu (oseltamivir).
Two distinct types of dehydroquinate dehydratases have been shown to catalyze the dehydration of dehydroquinate through disparate mechanisms. The protein we studied is representative of the type I enzyme, which is known to form Schiff base with the reaction intermediate. It has a typical TIM barrel fold with eight parallel beta strands, and active site located at the C-terminal ends of strands. The protein was co-crystallized with the 3-dehydroshikimate, which was found covalently bound to the highly conserved lysine in the active site. The reported structure represents the intermediate step in the dehydration of dehydroquinate to dehydroshikimate.