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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6345859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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