Cyclodipeptide oxidase is an enzyme filament

Area of Science:

• Biochemistry
• Enzymology
• Secondary Metabolite Biosynthesis

Background:

• Modified cyclic dipeptides are pharmacologically active secondary metabolites.
• Cyclodipeptide oxidases (CDOs) are enzymes involved in their biosynthesis, but their structures remain largely uncharacterized.

Approach:

• Structural characterization of the Streptomyces noursei enzyme AlbAB, a cyclodipeptide oxidase (CDO).
• Investigated the enzyme's oligomeric state, cofactor dependency, and the role of filament formation in its activity.
• Analyzed the conservation of protein-protein interactions within the enzyme complex.

Key Points:

• AlbAB forms a megadalton heterooligomeric enzyme filament composed of alternating AlbA and AlbB dimers.
• Enzyme activity is critically dependent on this filament formation.
• Highly conserved AlbA-AlbB interactions suggest that CDO-like enzymes generally function as filaments.

Conclusions:

• This study provides the first structural characterization of a cyclodipeptide oxidase (CDO).
• The findings elucidate the mechanism of CDO filament formation and its importance for enzymatic activity.
• Results offer valuable insights for future applications of CDOs in biocatalysis and chemoenzymatic synthesis of cyclic dipeptides.