title: New insights into the evolutionary links relating to the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase subfamilies.
abstract: Bacterial 3-deoxy-d-arabino-heptulosonate 7-phosphate synthases (DAHPSs) have been divided into either of two classes (Class I/Class II) or subfamilies (AroAI(alpha)/AroAI(beta)). Our investigation into the biochemical properties of the unique bifunctional DAHPS from Bacillus subtilis provides new insight into the evolutionary link among DAHPS subfamilies. In the present study, the DAHPS (aroA) and chorismate mutase (aroQ) activities of B. subtilis DAHPS are separated by domain truncation. Detailed enzymatic studies with the full-length wild-type protein and the truncated domains led to our hypothesis that the aroQ domain was fused to the N terminus of aroA in B. subtilis during evolution for the purpose of feedback regulation and not for the creation of a bona fide bifunctional enzyme. In addition, examination of aroA and aroQ fusion proteins from Porphyromonas gingivalis, in which the aroQ domain is fused to the C terminus of aroA, further supports the hypothesis. These results, along with sequence structure analysis of the DAHPS families suggest that "feedback regulation" may indeed be the evolutionary link between the two classes/subfamilies. It is likely that DAHPSs evolved from a primitive unregulated member of the AroAI(beta) subfamily. During evolution, some members of the AroAI(beta) subfamily remained unregulated, whereas other members acquired an extra domain for feedback regulation. The AroAI(alpha) subfamilies, however, evolved in a more complex manner to acquire insertions/extensions in the (beta/alpha)(8) barrel to function as regulatory elements.
authors.affiliation: Department of Medicinal Chemistry, University of Michigan, Ann Arbor, 48109-1065, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Woodard
mesh_terms: D010723:3-Deoxy-7-Phosphoheptulonate Synthase / Q000737:chemistry / Q000145:classification* / Q000378:metabolism; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology*; D001483:Base Sequence; D005075:Biological Evolution; D004492:Edetic Acid / Q000494:pharmacology; D025461:Feedback, Physiological; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008969:Molecular Sequence Data
chemical_list: D004492:Edetic Acid; D010723:3-Deoxy-7-Phosphoheptulonate Synthase