Acyltransferases Families in L-Methionine Biosynthesis

Proposition of functional re-annotation of metA and metX genes

Publication : Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis

Summary of our work : MetX and MetA are two phylogenetically unrelated protein families, but both are implied in the first step of the L-methionine biosynthesis pathway. MetX proteins are known as L-homoserine O-acetyltransferases (HAT), while MetA proteins are generally annotated as L-homoserine O-succinyltransferase (HST). Here we demonstrated that in vitro, over ~100 enzymes, that HAT and HST activities are actually widely observed in both families. In silico analysis of active site structures pointed out key residues specific to each activity. Thus, we reexamined nearly 10 000 MetA and MetX proteins using homology modeling and we corrected the function for about 60% of them. The mapping of these predictions on the NCBI taxonomy tree shows that ancestral MetX and MetA had both the same activity, and suggests that an evolutionary pressure led them to evolve toward HTS activity in proteobacteria (figure below a). We finally discovered that 10% of MetX are paralogs that participate in L-cysteine synthesis in fungi and probably in few gammaproteobacteria by forming the novel metabolite O-succinyl-L-serine (figure below b).

L-homoserine O-succinyltransferase (red) and L-serine O-succinyltransferase (green) activities experimentally proven and predicted in the Bacteria, Eukaryota and Archaea. The NCBI taxonomic cladogram is cut at the phylum level except for proteobacteria where the tree was cut at the class level.

Visit the tabs above to discover the activity (HST or HAT) we predict for metA and metX genes