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

Autor:	Yang G; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands., Pećanac O; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands., Wijma HJ; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands., Rozeboom HJ; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands., de Gonzalo G; Departamento de Química Orgánica, Universidad de Sevilla, and Centro de Innovación en Química Avanzada (ORFEO-CINQA), 41012 Sevilla, Spain., Fraaije MW; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands., Mascotti ML; Molecular Enzymology Group, University of Groningen, 9747 AG Groningen, the Netherlands; IMIBIO-SL CONICET, Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina. Electronic address: m.l.mascotti@rug.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114130. Date of Electronic Publication: 2024 Apr 18.
DOI:	10.1016/j.celrep.2024.114130
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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