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Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines

Although cyclic imines are present in various bioactive secondary metabolites, their degradative metabolism remains unknown. Here, we report that copper amine oxidases, which are important in metabolism of primary amines, catalyze a cyclic imine cleavage reaction. We isolate a microorganism (Arthrob...

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Autores principales: Nagakubo, Toshiki, Kumano, Takuto, Ohta, Takehiro, Hashimoto, Yoshiteru, Kobayashi, Michihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345859/
https://www.ncbi.nlm.nih.gov/pubmed/30679427
http://dx.doi.org/10.1038/s41467-018-08280-w
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author Nagakubo, Toshiki
Kumano, Takuto
Ohta, Takehiro
Hashimoto, Yoshiteru
Kobayashi, Michihiko
author_facet Nagakubo, Toshiki
Kumano, Takuto
Ohta, Takehiro
Hashimoto, Yoshiteru
Kobayashi, Michihiko
author_sort Nagakubo, Toshiki
collection PubMed
description Although cyclic imines are present in various bioactive secondary metabolites, their degradative metabolism remains unknown. Here, we report that copper amine oxidases, which are important in metabolism of primary amines, catalyze a cyclic imine cleavage reaction. We isolate a microorganism (Arthrobacter sp. C-4A) which metabolizes a β-carboline alkaloid, harmaline. The harmaline-metabolizing enzyme (HarA) purified from strain C-4A is found to be copper amine oxidase and catalyze a ring-opening reaction of cyclic imine within harmaline, besides oxidative deamination of amines. Growth experiments on strain C-4A and Western blot analysis indicate that the HarA expression is induced by harmaline. We propose a reaction mechanism of the cyclic imine cleavage by HarA containing a post-translationally-synthesized cofactor, topaquinone. Together with the above results, the finding of the same activity of copper amine oxidase from E. coli suggests that, in many living organisms, these enzymes may play crucial roles in metabolism of ubiquitous cyclic imines.
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spelling pubmed-63458592019-01-28 Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines Nagakubo, Toshiki Kumano, Takuto Ohta, Takehiro Hashimoto, Yoshiteru Kobayashi, Michihiko Nat Commun Article Although cyclic imines are present in various bioactive secondary metabolites, their degradative metabolism remains unknown. Here, we report that copper amine oxidases, which are important in metabolism of primary amines, catalyze a cyclic imine cleavage reaction. We isolate a microorganism (Arthrobacter sp. C-4A) which metabolizes a β-carboline alkaloid, harmaline. The harmaline-metabolizing enzyme (HarA) purified from strain C-4A is found to be copper amine oxidase and catalyze a ring-opening reaction of cyclic imine within harmaline, besides oxidative deamination of amines. Growth experiments on strain C-4A and Western blot analysis indicate that the HarA expression is induced by harmaline. We propose a reaction mechanism of the cyclic imine cleavage by HarA containing a post-translationally-synthesized cofactor, topaquinone. Together with the above results, the finding of the same activity of copper amine oxidase from E. coli suggests that, in many living organisms, these enzymes may play crucial roles in metabolism of ubiquitous cyclic imines. Nature Publishing Group UK 2019-01-24 /pmc/articles/PMC6345859/ /pubmed/30679427 http://dx.doi.org/10.1038/s41467-018-08280-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nagakubo, Toshiki
Kumano, Takuto
Ohta, Takehiro
Hashimoto, Yoshiteru
Kobayashi, Michihiko
Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title_full Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title_fullStr Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title_full_unstemmed Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title_short Copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
title_sort copper amine oxidases catalyze the oxidative deamination and hydrolysis of cyclic imines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345859/
https://www.ncbi.nlm.nih.gov/pubmed/30679427
http://dx.doi.org/10.1038/s41467-018-08280-w
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