Using Strictosidine Synthase to Prepare Novel Alkaloids

Author(s): Huajian Zhu, Petra Kercmar, Fangrui Wu, Chitra Rajendran, Lianli Sun, Meitian Wang, Joachim Stockigt

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 15 , 2015


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Abstract:

The Pictet-Spenglerase strictosidine synthase (STR) has been characterized as the central enzyme in the biosynthesis of around 2000 monoterpenoid indole alkaloids in plants. In the light of a high therapeutic value and huge scaffold diversity these alkaloids represent, STR as an enzyme has attracted great attentions in recent years, intending to be utilized in the formation of new interesting alkaloids with unusual substitution pattern or even with novel scaffolds. For outlining the application potential that STR possesses, together with insight into the reaction mechanism catalyzed by STR, strategies and methods for exploring the applicability of STR have been updated in this article by taking R. serpentina STR (RS-STR) and C. roseus. STR (CR-STR) as representative models, followed by introducing the latest released complex structures of RS-STR with new substrates. Examples provided here, including substrate scaffold tailoring, X-ray crystal complex structure comparison, protein engineering and biosynthetic pathway reprogramming, pave the way to finally construct novel alkaloids libraries by chemo-enzymatic approaches.

Keywords: Alkaloids, application strategies, protein engineering, strictosidine synthase, substrates, X-ray complex structures.

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Article Details

VOLUME: 22
ISSUE: 15
Year: 2015
Published on: 03 May, 2015
Page: [1880 - 1888]
Pages: 9
DOI: 10.2174/0929867322666150408110919
Price: $65

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