A role for Old Yellow Enzyme in ergot alkaloid biosynthesis
Johnathan Z Cheng1, Christine M Coyle, Daniel G Panaccione
1Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Journal of the American Chemical Society
|January 28, 2010
Summary
Filamentous fungi produce ergot alkaloids with diverse effects. Researchers identified a key enzyme in Aspergillus fumigatus that reduces an intermediate, enabling the formation of the ergot alkaloid D ring.
Area of Science:
- Biochemistry
- Mycology
- Natural Product Synthesis
Background:
- Ergot alkaloids are pharmacologically significant secondary metabolites from filamentous fungi.
- The complete biosynthetic pathways for ergot alkaloids remain incompletely understood.
- Understanding biosynthesis is crucial for potential pharmaceutical applications.
Purpose of the Study:
- To elucidate a key step in the biosynthesis of ergot alkaloids.
- To identify the enzyme responsible for a specific reduction reaction in the pathway.
- To understand the formation of the D ring in the ergot alkaloid structure.
Main Methods:
- Analysis of the Aspergillus fumigatus ergot gene cluster.
- Biochemical characterization of a homologous Old Yellow Enzyme.
- Enzymatic assays to determine substrate specificity and product formation.
Main Results:
- A homologue of Old Yellow Enzyme from Aspergillus fumigatus was identified.
- This enzyme catalyzes the reduction of the alpha,beta unsaturated alkene of chanoclavine-I aldehyde.
- The reduction product, dihydrochanoclavine aldehyde, facilitates D ring formation via intramolecular cyclization.
Conclusions:
- The identified enzyme plays a critical role in ergot alkaloid biosynthesis.
- This finding advances the understanding of the ergot alkaloid structural framework formation.
- Elucidation of this step provides insights into the natural product synthesis by fungi.
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