Diels–Alderases

Abstract

After representative examples of natural Diels–Alder adducts are introduced, controversial issues on the involvement of the biological Diels–Alder reaction are discussed on the basis of biomimetic synthesis. Natural Diels–Alder adducts may be obtained by enzymatic formation of reactive diene and dienophile. Intriguing cycloaddition may proceed either in the active site of the enzyme or after releasing it to the reaction media. Possible involvement of oxidases, polyketide synthases, and other miscellaneous enzymes in the Diels–Alder reaction is introduced on the basis of biomimetic synthesis. Apart from enzymes, there are several examples of other macromolecules such as catalytic antibodies and RNA that catalyze the Diels–Alder reaction. Their mechanisms are also discussed. Recent results on three Diels-Alderase, solanapyrone synthase, lovastatin synthase, and macrophomate synthase are described. Rapid progress in polyketide biosynthesis allowed identification of the biosynthetic gene clusters of several Diels–Alder adducts such as equisetin, chaetoglobosin, spinosyn, kijanimicin, and chlorothricin. Possible enzymes that catalyze the corresponding Diels–Alder reaction in the biosynthesis of these polyketides are introduced.