6533b828fe1ef96bd12877f1

RESEARCH PRODUCT

Diels-Alderase Catalyzing the Cyclization Step in the Biosynthesis of Spinosyn A

Luis R. DomingoLydia RhymanPonnadurai RamasamiJosé A. Sáez

subject

chemistry.chemical_classificationStrain (chemistry)biologyStereochemistryActive siteCatalysisEnzyme catalysischemistry.chemical_compoundEnzymeBiosynthesischemistrybiology.proteinLactoneDiels–Alder reaction

description

The conversion of putative macrocyclic lactone into the tricyclic compound, as a key step in the biosynthesis of spinosyn A , has been theoretically investigated using DFT methods. The relatively low activation free energy computed for the cyclization process of the actual macrocyclic lactone (21.0 kcal/mol) furnishes a rationalization for a spontaneous ( i.e. nonenzymatically catalyzed) cyclization process in the biosynthesis of spinosyn A . A geometric analysis of putative macrocyclic lactone indicates that a slight strain on the lactone at the active site of the SpnF gene could decrease the activation free energy to ca . 16 kcal/mol. This nonspecific participation of the enzyme, which accounts for the relatively low 500-fold acceleration that has been found in this gene, rules out the participation of a specific Diels-Alderase.

yearjournalcountryeditionlanguage
2015-01-01
https://doi.org/10.1016/b978-0-12-802508-6.00009-0