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Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis

Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that tak...

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Autores principales: Zou, Yi, Garcia-Borràs, Marc, Tang, Mancheng C., Hirayama, Yuichiro, Li, Dehai H., Li, Li, Watanabe, Kenji, Houk, K. N., Tang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310975/
https://www.ncbi.nlm.nih.gov/pubmed/28114276
http://dx.doi.org/10.1038/nchembio.2283
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author Zou, Yi
Garcia-Borràs, Marc
Tang, Mancheng C.
Hirayama, Yuichiro
Li, Dehai H.
Li, Li
Watanabe, Kenji
Houk, K. N.
Tang, Yi
author_facet Zou, Yi
Garcia-Borràs, Marc
Tang, Mancheng C.
Hirayama, Yuichiro
Li, Dehai H.
Li, Li
Watanabe, Kenji
Houk, K. N.
Tang, Yi
author_sort Zou, Yi
collection PubMed
description Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.
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spelling pubmed-53109752017-07-23 Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis Zou, Yi Garcia-Borràs, Marc Tang, Mancheng C. Hirayama, Yuichiro Li, Dehai H. Li, Li Watanabe, Kenji Houk, K. N. Tang, Yi Nat Chem Biol Article Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis. 2017-01-23 2017-03 /pmc/articles/PMC5310975/ /pubmed/28114276 http://dx.doi.org/10.1038/nchembio.2283 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zou, Yi
Garcia-Borràs, Marc
Tang, Mancheng C.
Hirayama, Yuichiro
Li, Dehai H.
Li, Li
Watanabe, Kenji
Houk, K. N.
Tang, Yi
Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title_full Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title_fullStr Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title_full_unstemmed Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title_short Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis
title_sort enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310975/
https://www.ncbi.nlm.nih.gov/pubmed/28114276
http://dx.doi.org/10.1038/nchembio.2283
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