The Claisen rearrangement of an unusual substrate in chorismate mutase

The calculated reaction path for an unusual substrate of chorismate mutase (Bacillus subtilis) is found to be completely comparable to that of the native chorismate. In the unusual substrate, the cyclohexadienyl ring in chorismate is replaced by dihydropyridine. Previous theoretical calculations of the native reaction path provide the basis for predicting that the interactions of the unusual reactant in the active site are electronically analogous to the native. Three unusual substrates are obtained by replacing each of the C-H moieties in the cyclohexadienyl ring by a nitrogen atom. This substitution does not substantially alter the electronic characteristics of the ring both with regard to the catalytic activation by the active site and the interaction with hydrophobic groups in the active site. The activation energies and optimized structures along the reaction path are obtained for the tautomers of the unusual reactant and product. The possibility of ultimately obtaining an unusual amino acid by this pathway is discussed.