A Pseudoisostructural Type II DAH7PS Enzyme from Pseudomonas aeruginosa: Alternative Evolutionary Strategies to Control Shikimate Pathway Flux

Biochemistry. 2018 May 8;57(18):2667-2678. doi: 10.1021/acs.biochem.8b00082. Epub 2018 Apr 16.


The shikimate pathway is responsible for the biosynthesis of key aromatic metabolites in microorganisms and plants. The enzyme 3-deoxy-d- arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step of the pathway and DAH7PSs are classified as either type I or type II. The DAH7PSs from Pseudomonas aeruginosa are of particular interest as open reading frames encoding four putative DAH7PS isoenzymes, two classified as type Iα and two classified as type II, have been identified. Here, the structure of a type II DAH7PS enzyme from P. aeruginosa (PAO1) has been determined at 1.54 Å resolution, in complex with its allosteric inhibitor tryptophan. Structural differences in the extra-barrel elements, when compared to other type II DAH7PS enzymes, directly relate to the formation of a distinct quaternary conformation with consequences for allosteric function and the control of flux to branching pathways. In contrast to the well-characterized Mycobacterium tuberculosis type II DAH7PS, which binds multiple allosteric inhibitors, this PaeDAH7PSPA2843 is observed to be modestly allosterically inhibited by a single aromatic amino acid, tryptophan. In addition, structures in complex with tyrosine or with no allosteric ligand bound were determined. These structures provide new insights into the linkages between the active and allosteric sites. With four putative DAH7PS enzymes, P. aeruginosa appears to have evolved control of shikimate pathway flux at the genetic level, rather than control by multiple allosteric effectors to a single type II DAH7PS, as in M. tuberculosis. Type II DAH7PSs, thus, appear to have a more varied evolutionary trajectory than previously indicated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Deoxy-7-Phosphoheptulonate Synthase / chemistry*
  • 3-Deoxy-7-Phosphoheptulonate Synthase / genetics
  • 3-Deoxy-7-Phosphoheptulonate Synthase / metabolism
  • Allosteric Regulation / genetics
  • Allosteric Site / genetics
  • Binding Sites
  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Metabolic Networks and Pathways / genetics
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology
  • Protein Binding
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / genetics
  • Shikimic Acid / chemistry
  • Shikimic Acid / metabolism*
  • Tryptophan / chemistry


  • Shikimic Acid
  • Tryptophan
  • 3-Deoxy-7-Phosphoheptulonate Synthase