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Computational Investigation of the Mechanism of Diels-Alderase PyrI4.

ABSTRACT: We studied the mechanisms of activation and stereoselectivity of a monofunctional Diels-Alderase (PyrI4)-catalyzed intramolecular Diels-Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique "lid" feature of PyrI4 to stabilize the Diels-Alder transition state. PyrI4 enhances the intrinsic Diels-Alder stereoselectivity of the substrate and leads to stereospecific formation of the product.

SUBMITTER: Zou Y

PROVIDER: S-EPMC9328771 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Computational Investigation of the Mechanism of Diels-Alderase PyrI4.

Zou Yike Y Yang Song S Sanders Jacob N JN Li Wei W Yu Peiyuan P Wang Hongbo H Tang Zhijun Z Liu Wen W Houk K N KN

Journal of the American Chemical Society 20201114 47

We studied the mechanisms of activation and stereoselectivity of a monofunctional Diels-Alderase (PyrI4)-catalyzed intramolecular Diels-Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique "lid" feature of PyrI4 to stabilize the Diels-Alder transition state. PyrI4 enhances the intrinsic Diels-A ...[more]

PMID: 33190496

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