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Pictet-Spenglerasestrictosidine synthase (STR) is key for plant monoterpenoid indole alkaloid biosynthesis. This review explores STR

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Area of Science:

  • Biochemistry and Molecular Biology
  • Natural Product Chemistry
  • Enzymology

Background:

  • Monoterpenoid indole alkaloids (MIAs) are a large class of plant-derived compounds with significant therapeutic value and structural diversity.
  • Pictet-Spenglerasestrictosidine synthase (STR) is the central enzyme catalyzing a key step in the biosynthesis of over 2000 known MIAs.
  • The therapeutic potential and structural complexity of MIAs drive interest in utilizing STR for novel alkaloid synthesis.

Purpose of the Study:

  • To review and update strategies for exploring the application potential of STR in synthesizing novel alkaloids.
  • To provide insights into the reaction mechanism catalyzed by STR.
  • To highlight methods for engineering STR and its substrates for generating diverse alkaloid scaffolds.

Main Methods:

  • Utilizing R. serpertina STR (RS-STR) and C. roseus STR (CR-STR) as representative models.
  • Analysis of latest complex structures of RS-STR with novel substrates.
  • Application of substrate scaffold tailoring, X-ray crystallography, protein engineering, and biosynthetic pathway reprogramming.

Main Results:

  • Detailed exploration of STR's role in MIA biosynthesis.
  • Presentation of new complex structures revealing substrate interactions.
  • Demonstration of successful protein engineering and pathway reprogramming strategies.

Conclusions:

  • STR is a versatile enzyme with significant potential for chemo-enzymatic synthesis of novel alkaloids.
  • Integration of structural biology, protein engineering, and synthetic biology approaches enables the construction of diverse alkaloid libraries.
  • These advancements pave the way for discovering new therapeutic agents and understanding plant secondary metabolism.