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

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Scheler U,Brandt W,Porzel A,Rothe K,Manzano D,Božić D,Papaefthimiou D,Balcke GU,Henning A,Lohse S,Marillonnet S,Kanellis AK,Ferrer A,Tissier A

doi

10.1038/ncomms12942

subject

Has Abstract

pub_date

2016-10-05 00:00:00

pages

12942

issn

2041-1723

pii

ncomms12942

journal_volume

7

pub_type

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