Enzyme - 3-deoxy-8-phosphooctulonate synthase

Alternative Name(s)
  • 2-dehydro-3-deoxy-D-octonate-8-phosphate D-arabinose-5-phosphate-lyase
  • 3-deoxy-D-manno-octulosonate-8-phosphate synthase.
  • KDOP synthase.
  • 2-keto-3-deoxy-8-phosphooctonic synthetase.
  • 3-deoxyoctulosonic 8-phosphate synthetase.
  • KDO-8-P synthase.
  • Phospho-2-keto-3-deoxyoctonate aldolase.
  • 3-deoxy-D-manno-octulosonic acid 8-phosphate synthetase.
  • (pyruvate-phosphorylating).
  • 3-deoxy-D-mannooctulosonate-8-phosphate synthetase.
  • KDO-8-phosphate synthetase.
  • 2-dehydro-3-deoxy-phosphooctonate aldolase.

Catalytic Activity

D-arabinose 5-phosphate + H2O + phosphoenolpyruvate = 3-deoxy-alpha-D-manno-2-octulosonate-8-phosphate + phosphate


There are no Cofactors for this Enzyme

Reaction Mechanism

    3-deoxy-d-manno-s-octulosonate-8-phosphate synthase from Escherichia coli (KDO8P) is responsible for the synthesis of the named product from Phosphenol Pyruvate (PEP) and arabinose-5-phosphate (A5P). It thus plays a role in the synthesis of complex lipids for the gram negative bacterial cell wall, so is a possible target for antibiotics. It displays homology with many PEP utilising enzymes, particularly the metal dependent enzyme DAHP synthase which works by a similar mechanism where a single amino acid change of non-metallo KDO8P changes it to metallo-KDO8P.

    The reaction proceeds through an aldol-like condensation where water activated phosphoenolpyruvate attacks A5P. This forms a bis-phosphorylated tetrahedral intermediate recorded in mass spectrometry experiments. The resulting intermediate then collapses, eliminating a phosphate group. Subsequent sugar cyclisation occurs to form KDO8P. By analogy with the Aquifex aeolicus metallo-KDO8P synthase, water by having hydrogen bonds with the phosphate on PEP increases it's nucleophilicity to attack PEP which in turn is positioned for nucleophilic attack by Lys60. Asp250 and Asn26 hydrogen bond and position A5P for the reaction. Asn26 is thought to mimic the metal ion in metallo-KDO8P enzymes.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asn P0A715 26 1q3n 26
    Lys P0A715 60 1q3n 60
    Asp P0A715 250 1q3n 250
    Step Components

    overall reactant used, proton transfer, overall product formed, unimolecular elimination by the conjugate base, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, intramolecular nucleophilic addition, intermediate collapse

    Step 1.

    Water acts as a nucleophile and attacks C2 on PEP, activating C3 PEP to attack the reducing end of A5P. The step passes through an oxocarbenium ion-like transition state.

    Step 2.

    Phosphohemiketal intermediate forms. The tetrahedral intermediate collapses to open chain KDO8P.

    Step 3.

    Sugar condensation to form the ring structure, 3-Deoxy-D-manno-octulosonate phosphate.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
2-dehydro-3-deoxyphosphooctonate aldolase 2 Mouse-ear cress
2-dehydro-3-deoxyphosphooctonate aldolase Escherichia coli (strain K12)
2-dehydro-3-deoxyphosphooctonate aldolase 1 Mouse-ear cress
2-dehydro-3-deoxyphosphooctonate aldolase isoform A Wild soybean
2-dehydro-3-deoxyphosphooctonate aldolase (Phospho-2-dehydro-3-deoxyoctonate aldolase) (3-deoxy-D-manno-octulosonic acid 8-phosphate synthetase) (KDO-8-phosphate synthetase) (KDO 8-P synthase) (KDOPS) mine drainage metagenome