Evolution of the catalytic mechanism at the dawn of the Baeyer-Villiger monooxygenases

YANG G; PECANAC O; WIJMA H; ROZEBOOM H; DE GONZALO G; FRAAIJE MW; MASCOTTI ML

Cell Reports

Cell

Año: 2024

Enzymes are crucial for the emergence and sustenance of life on earth. How they became catalyticallyactive during their evolution is still an open question. Two opposite explanations are plausible: acquiring amechanism in a series of discrete steps or all at once in a single evolutionary event. Here, we use molecularphylogeny, ancestral sequence reconstruction, and biochemical characterization to follow the evolution of aspecialized group of flavoproteinmonooxygenases, the bacterial Baeyer-Villigermonooxygenases (BVMOs).These enzymes catalyze an intricate chemical reaction relying on three different elements: a reduced nicotin-amide cofactor, dioxygen, and a substrate. Characterization of ancestral BVMOs shows that the catalyticmechanism evolved in a series of steps starting from a FAD-binding protein and further acquiring reactivityand specificity toward each of the elements participating in the reaction. Together, the results of our workportray how an intrinsically complex catalytic mechanism emerged during evolution.