Form follows function: structural and catalytic variation in the class a flavoprotein monooxygenases

Area of Science:

• Biochemistry
• Enzymology
• Molecular Biology

Background:

• Flavoprotein monooxygenases (FPMOs) catalyze substrate monooxygenation using flavin cofactors.
• FPMOs employ diverse mechanisms, including one- and two-component systems, for cofactor reduction and substrate oxygenation.

Purpose of the Study:

• To provide a detailed review of Class A flavoprotein hydroxylases (FPMOs).
• To contextualize Class A FPMOs within the broader FPMO classification (Classes B-F).
• To elucidate the complete catalytic cycle of Class A FPMOs.

Main Methods:

• Spectrophotometric kinetic methods to observe catalytic events.
• Structural data analysis to support mechanistic conclusions.
• Compilation of research on both established and novel Class A FPMO examples.

Main Results:

• Class A FPMOs are single-component enzymes with extensive research documentation.
• These enzymes utilize dynamic flavin ring movements for substrate access, cofactor interaction, and product release.
• Key catalytic steps are directly observable, providing detailed mechanistic insights.

Conclusions:

• Class A FPMOs exhibit sophisticated mechanisms for efficient monooxygenation.
• Flavin ring choreography is central to their catalytic strategy.
• This review synthesizes current knowledge for a comprehensive understanding of Class A FPMO function.