Using Strictosidine Synthase to Prepare Novel Alkaloids

Zhu, Huajian and Kercmar, Petra and Wu, Fangrui and Rajendran, Chitra and Sun, Lianli and Wang, Meitian and Stoeckigt, Joachim (2015) Using Strictosidine Synthase to Prepare Novel Alkaloids. CURRENT MEDICINAL CHEMISTRY, 22 (15). pp. 1880-1888. ISSN 0929-8673, 1875-533X

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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.

Item Type: Article
Uncontrolled Keywords: MONOTERPENOID INDOLE ALKALOIDS; RAUVOLFIA-SERPENTINA; BENZYLISOQUINOLINE ALKALOIDS; SUBSTRATE-SPECIFICITY; CATHARANTHUS-ROSEUS; ENZYMATIC FORMATION; COMPOUND LIBRARIES; ESCHERICHIA-COLI; KEY INTERMEDIATE; NATURAL-PRODUCTS; Alkaloids; application strategies; protein engineering; strictosidine synthase; substrates; X-ray complex structures
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 31 Jul 2019 08:54
Last Modified: 31 Jul 2019 09:00
URI: https://pred.uni-regensburg.de/id/eprint/6249

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