3 years ago

Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis

Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis
Véronique de Berardinis, Jean Weissenbach, Marielle Besnard-Gonnet, Anne Zaparucha, David Vallenet, Pascal Bazire, François Artiguenave, Virginie Pellouin, Jean-Louis Petit, Karine Bastard, Carine Vergne-Vaxelaire, Adrien Debard, Ekaterina Darii, Marcel Salanoubat, Antoine Danchin, Claudine Médigue, Agnès Pinet-Turpault, Alain Perret, Clémence Brewee, Thomas Bessonnet, Aline Mariage
Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetX and MetA enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively. We determined the enzymatic activities of 100 enzymes from diverse species, and interpreted the results by structural classification of active sites based on protein structure modeling. We predict that >60% of the 10,000 sequences from these families currently present in databases are incorrectly annotated, and suggest that acetyl-CoA was originally the sole substrate of these isofunctional enzymes, which evolved to use exclusively succinyl-CoA in the most recent bacteria. We also uncovered a divergent subgroup of MetX enzymes in fungi that participate only in L-cysteine biosynthesis as O-succinyl-L-serine transferases.

Publisher URL: http://dx.doi.org/10.1038/nchembio.2397

DOI: 10.1038/nchembio.2397

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