Chopping and Changing: the Evolution of the Flavin-dependent Monooxygenases

Area of Science:

• Biochemistry and Molecular Biology
• Enzymology
• Evolutionary Biology

Background:

• Flavin-dependent monooxygenases are vital enzymes with diverse physiological roles and biotechnological applications.
• These enzymes are categorized into eight classes (A-H) based on sequence and biochemical characteristics.

Purpose of the Study:

• To investigate the evolutionary history of flavin-dependent monooxygenase classes A, B, E, F, and G.
• To understand the mechanisms driving the divergence and functional evolution within these enzyme classes.

Main Methods:

• Combined structural and sequence analysis.
• Phylogenetic inference to reconstruct evolutionary relationships.
• Analysis of multidomain architectures and cofactor-binding domains.

Main Results:

• Multidomain architectures correlate with phylogenetic relationships, indicating domain recruitment as a key divergence driver.
• Functional divergence within classes is attributed to mechanisms like single-point mutations.
• The flavin adenine dinucleotide-binding domain is split in all studied classes, highlighting a conserved evolutionary feature.

Conclusions:

• The evolution of flavin-dependent monooxygenase classes is shaped by domain recruitment and subsequent modifications.
• Cofactor binding represents a significant constraint in the evolution of these enzymes.
• A complex series of evolutionary events led to the origin of the distinct classes within this enzyme family.