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

Stavrinides, A., Tatsis, E. C., Caputi, L., Foureau, E., Stevenson, C. E. M., Lawson, D. M., et al. (2016). Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity. Nature Communications, 7: 12116. doi:10.1038/ncomms12116.

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http://dx.doi.org/10.1038/ncomms12116 (Publisher version)
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 Creators:
Stavrinides, Anna, Author
Tatsis, Evangelos C., Author
Caputi, Lorenzo1, Author              
Foureau, Emilien, Author
Stevenson, Clare E. M., Author
Lawson, David M., Author
Courdavault, Vincent, Author
O'Connor, Sarah E.1, Author              
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1external, ou_persistent22              

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Free keywords: MACROMOLECULAR CRYSTALLOGRAPHY; CATHARANTHUS-ROSEUS; INDOLE ALKALOIDS; ALCOHOL-DEHYDROGENASE; ALMITRINE-RAUBASINE; BIOSYNTHESIS; ALSTONINE; SOFTWARE; STRICTOSIDINE; SEQUENCEScience & Technology - Other Topics;
 Abstract: Plants produce an enormous array of biologically active metabolites, often with stereo-chemical 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.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: SOC062
DOI: 10.1038/ncomms12116
 Degree: -

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 7 Sequence Number: 12116 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723