Structure, mechanism, and evolution of the last step in vitamin C biosynthesis.

Autor: Boverio A; Molecular Enzymology group, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands.; Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100, Pavia, Italy., Jamil N; Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100, Pavia, Italy., Mannucci B; Centro Grandi Strumenti, University of Pavia, Via Bassi 21, 27100, Pavia, Italy., Mascotti ML; Molecular Enzymology group, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands. mlmascotti@mendoza-conicet.gob.ar.; IMIBIO-SL CONICET, Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina. mlmascotti@mendoza-conicet.gob.ar.; Instituto de Histología y Embriología de Mendoza (IHEM)-CONICET-Universidad Nacional de Cuyo, 5500, Mendoza, Argentina. mlmascotti@mendoza-conicet.gob.ar., Fraaije MW; Molecular Enzymology group, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands. m.w.fraaije@rug.nl., Mattevi A; Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100, Pavia, Italy. andrea.mattevi@unipv.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 16; Vol. 15 (1), pp. 4158. Date of Electronic Publication: 2024 May 16.
DOI: 10.1038/s41467-024-48410-1
Abstrakt: Photosynthetic organisms, fungi, and animals comprise distinct pathways for vitamin C biosynthesis. Besides this diversity, the final biosynthetic step consistently involves an oxidation reaction carried out by the aldonolactone oxidoreductases. Here, we study the origin and evolution of the diversified activities and substrate preferences featured by these flavoenzymes using molecular phylogeny, kinetics, mutagenesis, and crystallographic experiments. We find clear evidence that they share a common ancestor. A flavin-interacting amino acid modulates the reactivity with the electron acceptors, including oxygen, and determines whether an enzyme functions as an oxidase or a dehydrogenase. We show that a few side chains in the catalytic cavity impart the reaction stereoselectivity. Ancestral sequence reconstruction outlines how these critical positions were affixed to specific amino acids along the evolution of the major eukaryotic clades. During Eukarya evolution, the aldonolactone oxidoreductases adapted to the varying metabolic demands while retaining their overarching vitamin C-generating function.
(© 2024. The Author(s).)
Databáze: MEDLINE
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