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

Alessandro Boverio, Neelam Jamil, Barbara Mannucci, Maria Laura Mascotti*, Marco W Fraaije*, Andrea Mattevi*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

16 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummer4158
Aantal pagina's10
TijdschriftNature Communications
Volume15
Nummer van het tijdschrift1
DOI's
StatusPublished - 16-mei-2024

Vingerafdruk

Duik in de onderzoeksthema's van 'Structure, mechanism, and evolution of the last step in vitamin C biosynthesis'. Samen vormen ze een unieke vingerafdruk.

Citeer dit