Divergent evolution of a Rossmann fold and identification of its oldest surviving ancestor

β-ketoacyl (acyl carrier protein) reductase (β-k-ACPR) enzymes are essential to fatty acid synthesis in bacteria. The analyses revealed the most primitive member of the β-k-ACPRs family was a NADP reductase where NADP was recognised by a Thr residue in the β2a3 turn. Aromatic residue stacking at the dimer interface and a previously undetected conserved sequence at the C-terminus, stabilise the oligomeric assembly of these proteins.Our analysis indicates that the primordial members of the β-k-ACPR family probably arose in the a-proteobacteria and are characterised by the presence of multiple open reading frames and an extreme codon and amino acid bias.