Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast

Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic p...

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Autores principales: Scheler, Ulschan, Brandt, Wolfgang, Porzel, Andrea, Rothe, Kathleen, Manzano, David, Božić, Dragana, Papaefthimiou, Dimitra, Balcke, Gerd Ulrich, Henning, Anja, Lohse, Swanhild, Marillonnet, Sylvestre, Kanellis, Angelos K., Ferrer, Albert, Tissier, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059481/
https://www.ncbi.nlm.nih.gov/pubmed/27703160
http://dx.doi.org/10.1038/ncomms12942
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author Scheler, Ulschan
Brandt, Wolfgang
Porzel, Andrea
Rothe, Kathleen
Manzano, David
Božić, Dragana
Papaefthimiou, Dimitra
Balcke, Gerd Ulrich
Henning, Anja
Lohse, Swanhild
Marillonnet, Sylvestre
Kanellis, Angelos K.
Ferrer, Albert
Tissier, Alain
author_facet Scheler, Ulschan
Brandt, Wolfgang
Porzel, Andrea
Rothe, Kathleen
Manzano, David
Božić, Dragana
Papaefthimiou, Dimitra
Balcke, Gerd Ulrich
Henning, Anja
Lohse, Swanhild
Marillonnet, Sylvestre
Kanellis, Angelos K.
Ferrer, Albert
Tissier, Alain
author_sort Scheler, Ulschan
collection PubMed
description Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic acid and its reconstitution in yeast cells. Cytochrome P450 oxygenases (CYP76AH22-24) from Rosmarinus officinalis and Salvia fruticosa already characterized as ferruginol synthases are also able to produce 11-hydroxyferruginol. Modelling-based mutagenesis of three amino acids in the related ferruginol synthase (CYP76AH1) from S. miltiorrhiza is sufficient to convert it to a 11-hydroxyferruginol synthase (HFS). The three sequential C20 oxidations for the conversion of 11-hydroxyferruginol to carnosic acid are catalysed by the related CYP76AK6-8. The availability of the genes for the biosynthesis of carnosic acid opens opportunities for the metabolic engineering of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti-inflammatory and anti-tumour activities.
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spelling pubmed-50594812016-10-26 Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast Scheler, Ulschan Brandt, Wolfgang Porzel, Andrea Rothe, Kathleen Manzano, David Božić, Dragana Papaefthimiou, Dimitra Balcke, Gerd Ulrich Henning, Anja Lohse, Swanhild Marillonnet, Sylvestre Kanellis, Angelos K. Ferrer, Albert Tissier, Alain Nat Commun Article Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic acid and its reconstitution in yeast cells. Cytochrome P450 oxygenases (CYP76AH22-24) from Rosmarinus officinalis and Salvia fruticosa already characterized as ferruginol synthases are also able to produce 11-hydroxyferruginol. Modelling-based mutagenesis of three amino acids in the related ferruginol synthase (CYP76AH1) from S. miltiorrhiza is sufficient to convert it to a 11-hydroxyferruginol synthase (HFS). The three sequential C20 oxidations for the conversion of 11-hydroxyferruginol to carnosic acid are catalysed by the related CYP76AK6-8. The availability of the genes for the biosynthesis of carnosic acid opens opportunities for the metabolic engineering of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti-inflammatory and anti-tumour activities. Nature Publishing Group 2016-10-05 /pmc/articles/PMC5059481/ /pubmed/27703160 http://dx.doi.org/10.1038/ncomms12942 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Scheler, Ulschan
Brandt, Wolfgang
Porzel, Andrea
Rothe, Kathleen
Manzano, David
Božić, Dragana
Papaefthimiou, Dimitra
Balcke, Gerd Ulrich
Henning, Anja
Lohse, Swanhild
Marillonnet, Sylvestre
Kanellis, Angelos K.
Ferrer, Albert
Tissier, Alain
Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title_full Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title_fullStr Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title_full_unstemmed Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title_short Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
title_sort elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059481/
https://www.ncbi.nlm.nih.gov/pubmed/27703160
http://dx.doi.org/10.1038/ncomms12942
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