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Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation

Novofumigatonin (1), isolated from the fungus Aspergillus novofumigatus, is a heavily oxygenated meroterpenoid containing a unique orthoester moiety. Despite the wide distribution of orthoesters in nature and their biological importance, little is known about the biogenesis of orthoesters. Here we s...

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Autores principales: Matsuda, Yudai, Bai, Tongxuan, Phippen, Christopher B. W., Nødvig, Christina S., Kjærbølling, Inge, Vesth, Tammi C., Andersen, Mikael R., Mortensen, Uffe H., Gotfredsen, Charlotte H., Abe, Ikuro, Larsen, Thomas O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030086/
https://www.ncbi.nlm.nih.gov/pubmed/29968715
http://dx.doi.org/10.1038/s41467-018-04983-2
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author Matsuda, Yudai
Bai, Tongxuan
Phippen, Christopher B. W.
Nødvig, Christina S.
Kjærbølling, Inge
Vesth, Tammi C.
Andersen, Mikael R.
Mortensen, Uffe H.
Gotfredsen, Charlotte H.
Abe, Ikuro
Larsen, Thomas O.
author_facet Matsuda, Yudai
Bai, Tongxuan
Phippen, Christopher B. W.
Nødvig, Christina S.
Kjærbølling, Inge
Vesth, Tammi C.
Andersen, Mikael R.
Mortensen, Uffe H.
Gotfredsen, Charlotte H.
Abe, Ikuro
Larsen, Thomas O.
author_sort Matsuda, Yudai
collection PubMed
description Novofumigatonin (1), isolated from the fungus Aspergillus novofumigatus, is a heavily oxygenated meroterpenoid containing a unique orthoester moiety. Despite the wide distribution of orthoesters in nature and their biological importance, little is known about the biogenesis of orthoesters. Here we show the elucidation of the biosynthetic pathway of 1 and the identification of key enzymes for the orthoester formation by a series of CRISPR-Cas9-based gene-deletion experiments and in vivo and in vitro reconstitutions of the biosynthesis. The novofumigatonin pathway involves endoperoxy compounds as key precursors for the orthoester synthesis, in which the Fe(II)/α-ketoglutarate-dependent enzyme NvfI performs the endoperoxidation. NvfE, the enzyme catalyzing the orthoester synthesis, is an Fe(II)-dependent, but cosubstrate-free, endoperoxide isomerase, despite the fact that NvfE shares sequence homology with the known Fe(II)/α-ketoglutarate-dependent dioxygenases. NvfE thus belongs to a class of enzymes that gained an isomerase activity by losing the α-ketoglutarate-binding ability.
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spelling pubmed-60300862018-07-05 Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation Matsuda, Yudai Bai, Tongxuan Phippen, Christopher B. W. Nødvig, Christina S. Kjærbølling, Inge Vesth, Tammi C. Andersen, Mikael R. Mortensen, Uffe H. Gotfredsen, Charlotte H. Abe, Ikuro Larsen, Thomas O. Nat Commun Article Novofumigatonin (1), isolated from the fungus Aspergillus novofumigatus, is a heavily oxygenated meroterpenoid containing a unique orthoester moiety. Despite the wide distribution of orthoesters in nature and their biological importance, little is known about the biogenesis of orthoesters. Here we show the elucidation of the biosynthetic pathway of 1 and the identification of key enzymes for the orthoester formation by a series of CRISPR-Cas9-based gene-deletion experiments and in vivo and in vitro reconstitutions of the biosynthesis. The novofumigatonin pathway involves endoperoxy compounds as key precursors for the orthoester synthesis, in which the Fe(II)/α-ketoglutarate-dependent enzyme NvfI performs the endoperoxidation. NvfE, the enzyme catalyzing the orthoester synthesis, is an Fe(II)-dependent, but cosubstrate-free, endoperoxide isomerase, despite the fact that NvfE shares sequence homology with the known Fe(II)/α-ketoglutarate-dependent dioxygenases. NvfE thus belongs to a class of enzymes that gained an isomerase activity by losing the α-ketoglutarate-binding ability. Nature Publishing Group UK 2018-07-03 /pmc/articles/PMC6030086/ /pubmed/29968715 http://dx.doi.org/10.1038/s41467-018-04983-2 Text en © The Author(s) 2018 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
Matsuda, Yudai
Bai, Tongxuan
Phippen, Christopher B. W.
Nødvig, Christina S.
Kjærbølling, Inge
Vesth, Tammi C.
Andersen, Mikael R.
Mortensen, Uffe H.
Gotfredsen, Charlotte H.
Abe, Ikuro
Larsen, Thomas O.
Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title_full Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title_fullStr Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title_full_unstemmed Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title_short Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
title_sort novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030086/
https://www.ncbi.nlm.nih.gov/pubmed/29968715
http://dx.doi.org/10.1038/s41467-018-04983-2
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