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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Detalhes bibliográficos
Autores: Scheler, Ulschan, Brandt, Wolfgang, Porzel, Andrea, Rothe, Kathleen, Manzano Alías, David, Bozic, Dragana, Papaefthimiou, Dimitra, Balcke, Gerd Ulrich, Henning, Anja, Lohse, Swanhild, Marillonnet, Sylvestre, Kanellis, Angelos K., Ferrer i Prats, Albert, Tissier, Alain
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2016
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/104313
Acesso em linha:https://hdl.handle.net/2445/104313
Access Level:Acceso aberto
Palavra-chave:Additius alimentaris
Llevats (Botànica)
Biosíntesi
Food additives
Yeast fungi
Biosynthesis
Descrição
Resumo: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.