Concerted, highly asynchronous, enzyme-catalyzed [4 + 2] cycloaddition in the biosynthesis of spinosyn A; computational evidence.

Hess BA, Smentek L
Org Biomol Chem. 2012 10 (37): 7503-9

PMID: 22885939 · DOI:10.1039/c2ob25827g

A theoretical study has been carried out on model systems to study a recently reported, (Nature, 2011, 473, 109) biosynthetic, [4 + 2] cycloaddition catalyzed by a stand-alone enzyme (the cyclase SpnF). It was suggested in this paper that SpnF is the first known example of a Diels-Alderase (DA). In the present study, for a model system of the substrate a transition structure was found with density functional calculations (DFT). In addition, the intrinsic reaction coordinate calculations indicated that the transition structure is that of a concerted, but highly asynchronous, DA reaction. Based on the DFT and Møller-Plesset second order calculations the activation energy was estimated to be about 15 kcal mol(-1). The results of a natural population analysis indicated that there is significant charge transfer in the transition state, and it is proposed that possibly the enzyme plays a dual role of not only folding the substrate into the proper conformation for the DA reaction to occur, but also lowering its activation energy by stabilization of the highly polarized transition structure.

MeSH Terms (6)

Biocatalysis Cyclization Macrolides Phosphorus-Oxygen Lyases Quantum Theory Saccharopolyspora

Connections (1)

This publication is referenced by other Labnodes entities: