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Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.

ABSTRACT: Cardenolides are specialized, steroidal metabolites produced in a wide array of plant families^1,2. 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 diseases^3-9. 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 β-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.

SUBMITTER: Kunert M

PROVIDER: S-EPMC10581899 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.

Kunert Maritta M Langley Chloe C Lucier Rosalind R Ploss Kerstin K Rodríguez López Carlos E CE Serna Guerrero Delia A DA Rothe Eva E O'Connor Sarah E SE Sonawane Prashant D PD

Nature plants 20230918 10

Cardenolides are specialized, steroidal metabolites produced in a wide array of plant families<sup>1,2</sup>. 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 diseases<sup>3-9</sup>. However, it is still unknown how plants synthesize 'high-value', complex cardenolide structures from, presumably, a sterol precursor. He ...[more]

PMID: 37723202

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Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.

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Promiscuous CYP87A enzyme activity initiates cardenolide biosynthesis in plants.

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