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  Redesign of a central enzyme in alkaloid biosynthesis

Chen, S., Galan, M. C., Coltharp, C., & O'Connor, S. E. (2006). Redesign of a central enzyme in alkaloid biosynthesis. Chemistry & Biology, 13(11), 1137-1141. doi:10.1016/j.chembiol.2006.10.009.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0002-A53B-2 Version Permalink: https://hdl.handle.net/21.11116/0000-0009-3D7F-6
Genre: Journal Article

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SOC010.pdf (Publisher version), 345KB
 
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SOC010s1.pdf (Supplementary material), 569KB
 
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 Creators:
Chen, Shi1, Author
Galan, M. Carmen1, Author
Coltharp, Carla1, Author
O'Connor, Sarah E.1, Author           
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1external, ou_persistent22              

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Free keywords: STRICTOSIDINE SYNTHASE; CATHARANTHUS-ROSEUS; INDOLE ALKALOIDS; SECOLOGANIN; CHEMISTRY; PURIFICATION; RAUVOLFIA; PRECURSOR; BIOLOGYBiochemistry & Molecular Biology;
 Abstract: Plant alkaloids exhibit a diverse array of structures and pharmaceutical activities, though metabolic engineering efforts in these eukaryotic pathways have been limited. Strictosidine synthase (STR) is the first committed step in the biosynthesis of over two thousand terpene indole alkaloids. We describe a rational redesign of the STR binding pocket to selectively accommodate secologanin substrate analogs. The mutant is selective for a substrate that can be chemoselectively derivatized. Evidence that this substrate can be processed by later steps of the terpene indole alkaloid pathway is provided. The work demonstrates that the central enzyme of this alkaloid pathway can be redesigned and that the pathway can turn over the unnatural intermediate that is generated. Modulation of the substrate specificity of enzymes of this complex pathway is therefore likely to enable metabolic engineering efforts of these alkaloids.

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Language(s): eng - English
 Dates: 2006
 Publication Status: Issued
 Pages: 5
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: SOC010
DOI: 10.1016/j.chembiol.2006.10.009
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Title: Chemistry & Biology
  Other : Chem. Biol.
Source Genre: Journal
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Publ. Info: London : Cell Press
Pages: - Volume / Issue: 13 (11) Sequence Number: - Start / End Page: 1137 - 1141 Identifier: ISSN: 1074-5521
CoNE: https://pure.mpg.de/cone/journals/resource/954925604781