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Updated: May 29, 2025
11:04
Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
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Molecular basis for azetidine-2-carboxylic acid biosynthesis
Tim J Klaubert1, Jonas Gellner1,2, Charles Bernard3,4
1Center for Protein Assemblies, Department Bioscience, School of Natural Sciences, Technical University Munich, Garching, Germany.
Nature Communications
|February 5, 2025
Summary
Azetidine-2-carboxylic acid (AZE) synthases catalyze S-adenosylmethionine cyclization. This study reveals catalytic mechanisms and uncovers broader prevalence of AZE-containing metabolites, enabling new biosynthesis applications.
Area of Science:
- Biochemistry
- Organic Chemistry
- Metabolomics
Background:
- Azetidine-2-carboxylic acid (AZE) is a plant metabolite.
- AZE synthases are involved in bacterial natural product pathways.
- These enzymes catalyze the cyclization of S-adenosylmethionine (SAM).
Purpose of the Study:
- To elucidate the catalytic mechanisms of AZE synthases.
- To investigate the prevalence of AZE-containing metabolites.
- To explore AZE's potential in combinatorial biosynthesis.
Main Methods:
- Structural and biochemical analyses.
- Quantum mechanical calculations.
- Mutagenesis studies.
- Combinatorial biosynthesis engineering.
Main Results:
- Detailed catalytic insights into AZE synthases were revealed.
- Substrate conformation, desolvation, and cation-π interactions facilitate SAM cyclization.
- Related SAM lyases were identified across diverse bacterial phyla.
- Engineered azabicyclene analogues were produced by introducing AZE synthase into the pyrrolizixenamide pathway.
Conclusions:
- A molecular framework for understanding SAM-dependent cyclization reactions was established.
- A wider prevalence of AZE-containing metabolites is suggested.
- AZE synthases offer potential for novel metabolite engineering.
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