Origin and evolution of one of the most ancient Rossmann folds

Abstract

The β‐ketoacyl [acyl carrier protein] reductase (β‐k‐ACPR) enzymes, a 690‐member subset of the SCOR short‐chain oxidoreductase family, are essential to fatty acid synthesis in bacteria and plants. There is one member of the family in every bacterial and archeal genome sequenced to date. We have discovered that (1) the most primitive member of the family was an NADP reductase, (2) that NADP binding was originally contingent upon a Ser or Thr residue in a specific turn, (3) that a specific dimer assembly is stabilized by the stacking of aromatic groups and (4) that a previously undetected GGMXM sequence at the C‐terminus, conserved in all species of proteobacteria, stabilizes the functionally required tetramer by multiple hydrogen bonding and aromatic ring stacking crosslinking the four monomers together. Our analysis indicates that the primordial members of the β‐k‐ACPR family probably arose in the GC‐rich α‐proteobacteria and that they are distinguished by the presence of multiple open reading frames (MORFs), an extreme codon bias in their DNA and an amino acid bias in their protein composition. This research was supported by NIH grant No. DK26546.