Structure-Based Engineering of Strictosidine Synthase: Auxiliary for Alkaloid Libraries

Elke A. Loris, Santosh Panjikar, Martin Ruppert, Leif Barleben, Matthias Unger, Helmut Schübel, Joachim Stöckigt

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

Abstract

The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.

Original languageEnglish
Pages (from-to)979-985
Number of pages7
JournalChemistry and Biology
Volume14
Issue number9
DOIs
Publication statusPublished - 21 Sep 2007
Externally publishedYes

Keywords

  • CHEMBIOL
  • MICROBIO

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