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Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.
Kunert, Maritta; Langley, Chloe; Lucier, Rosalind; Ploss, Kerstin; Rodríguez López, Carlos E; Serna Guerrero, Delia A; Rothe, Eva; O'Connor, Sarah E; Sonawane, Prashant D.
Afiliação
  • Kunert M; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Langley C; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Lucier R; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Ploss K; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Rodríguez López CE; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Serna Guerrero DA; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • Rothe E; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
  • O'Connor SE; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany. oconnor@ice.mpg.de.
  • Sonawane PD; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany. psonawane@ice.mpg.de.
Nat Plants ; 9(10): 1607-1617, 2023 10.
Article em En | MEDLINE | ID: mdl-37723202
Cardenolides are specialized, steroidal metabolites produced in a wide array of plant families1,2. Cardenolides play protective roles in plants, but these molecules, including digoxin from foxglove (Digitalis spp.), are better known for treatment of congenital heart failure, atrial arrhythmia, various cancers and other chronic diseases3-9. However, it is still unknown how plants synthesize 'high-value', complex cardenolide structures from, presumably, a sterol precursor. Here we identify two cytochrome P450, family 87, subfamily A (CYP87A) enzymes that act on both cholesterol and phytosterols (campesterol and ß-sitosterol) to form pregnenolone, the first committed step in cardenolide biosynthesis in the two phylogenetically distant plants Digitalis purpurea and Calotropis procera. Arabidopsis plants overexpressing these CYP87A enzymes ectopically accumulated pregnenolone, whereas silencing of CYP87A in D. purpurea leaves by RNA interference resulted in substantial reduction of pregnenolone and cardenolides. Our work uncovers the key entry point to the cardenolide pathway, and expands the toolbox for sustainable production of high-value plant steroids via synthetic biology.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cardenolídeos / Digitalis Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cardenolídeos / Digitalis Idioma: En Ano de publicação: 2023 Tipo de documento: Article