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

Guang Yang, Ognjen Pećanac, Hein J Wijma, Henriëtte J Rozeboom, Gonzalo de Gonzalo, Marco W Fraaije, Maria Laura Mascotti*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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

Original languageEnglish
Article number114130
Number of pages15
JournalCell reports
Volume43
Issue number5
Early online date18-Apr-2024
DOIs
Publication statusPublished - 28-May-2024

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