Class A flavoprotein monooxygenases: Checkpoint and new horizons

Area of Science:

• Biocatalysis and Sustainable Chemistry
• Enzymology
• Structural Biology

Background:

• Flavoprotein monooxygenases (FPMOs) are essential enzymes for oxyfunctionalization.
• Class A FPMOs are well-studied but underutilized for novel biocatalysis.
• Sustainable chemistry relies on efficient enzymatic catalysts.

Purpose of the Study:

• To provide an updated overview of Class A FPMOs using a structural biology approach.
• To systematically categorize known Class A FPMOs and their reaction diversity.
• To propose strategies for discovering novel FPMO biocatalysts.

Main Methods:

• Structural biology analysis of Class A FPMOs.
• Biochemical categorization of enzymes (prototypical vs. atypical).
• Review of cofactor preferences and protein engineering.

Main Results:

• Detailed discussion of Class A FPMO structure and catalytic mechanisms.
• Systematic overview of known Class A FPMOs, highlighting diverse reactions from similar scaffolds.
• Exploration of cofactor preferences and protein engineering applications.

Conclusions:

• Significant untapped potential exists within Class A FPMOs for biocatalysis.
• Understanding enzyme structure and function is key to unlocking new catalytic activities.
• A strategic approach can facilitate the discovery of novel FPMO biocatalysts for sustainable chemistry.