Publication

Article Metrics

Citations


Online attention

Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity

DOI: 10.1038/ncomms12116 DOI Help

Authors: Anna Stavrinides (The John Innes Centre) , Evangelos C. Tatsis (The John Innes Centre) , Lorenzo Caputi (The John Innes Centre) , Emilien Foureau (Université François-Rabelais de Tours, EA2106 ‘Biomolécules et Biotechnologies Végétales) , Clare E. M. Stevenson (The John Innes Centre) , David M. Lawson (The John Innes Centre) , Vincent Courdavault (Université François-Rabelais de Tours, EA2106 ‘Biomolécules et Biotechnologies Végétales') , Sarah E. O'Connor (The John Innes Centre)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 7

State: Published (Approved)
Published: July 2016
Diamond Proposal Number(s): 9475

Open Access Open Access

Abstract: Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold.

Journal Keywords: Biological sciences; Biochemistry; Molecular biology; Plant sciences

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Added On: 12/09/2016 14:05

Documents:
ncomms12116.pdf

Discipline Tags:

Plant science Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)