Enzyme - Holo-[acyl-carrier-protein] synthase

Alternative Name(s)
  • Acyl carrier protein holoprotein (holo-ACP) synthetase.
  • Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl
  • transferase.
  • 4'-phosphopantetheinyl transferase.
  • Acyl carrier protein synthetase.
  • L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl
  • Holo-ACP synthetase.
  • Holosynthase.
  • PPTase.
  • Holo-ACP synthase.
  • P-pant transferase.
  • ACPS.
  • Acyl carrier protein synthase.

Catalytic Activity

po-[ACP] + CoA = adenosine 3',5'-bisphosphate + H(+) + holo-[ACP]



Reaction Mechanism

    Holo-(acyl carrier protein) synthase (AcpS) from Bacillus subtilis is a member of the phosphopantetheinyl transferase superfamily. AcpS post-translationally modifies ACP to its holo form in order to activate it. AcpS catalyses the transfer of the 4'-phosphopantetheinyl (P-pant) moiety of coenzyme A to a serine residue on the ACP. This gives the activated ACP enzyme and Adenosine 3'5'-bisphosphate as products. This process is important as ACP enzymes play important roles in a number of biosynthetic pathways, such as the synthesis of fatty acids, vitamins, AcpS is essential in the initiation of the biosynthesis of fatty acids, polyketide antibiotics and non-ribosomal peptides.

    This enzyme requires either Mg(II) or Mn(II) for activity. The mechanism proceeds as follows: Asp 35 (in the substrate protein) deprotonates a water molecule. This activated water molecule then acts as a general base by deprotonating the substrate serine residue, activating it for nucleophilic attack on the beta-phosphate of CoA. The nucleophilic attack results in the transfer of the phosphopantetheinyl group to the substrate serine residue. The resulting negatively charged 3',5'-ADP is stabilised by interactions with Lys 62, the mainchain amide of His 105 and the magnesium ion. A proton is then transferred to 3',5'-ADP from either a water molecule or Lys 62.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    His P96618 105 1f80 104
    Lys P96618 62 1f80 61
    Asp P80643 36 1f80 40
    Step Components

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

    Step 1.

    Magnesium activated water deprotonates the Apo-ACP, activating it.

    Step 2.

    The activated Apo-ACP attacks the CoA in a nucleophilic addition, creating a pentavalent phosphate intermediate.

    Step 3.

    The pentavalent phosphate intermediate collapses, initiating an elimination of the adenosine 3',5'-bisphosphate product, which is reprotonated from a water molecule.


    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Pseudomonas putida 3.3 CoA-[4'-phosphopantetheine] in 100 mM Tris-HCl, pH 7.8, at 30°C
    Bacillus subtilis 3.5 CoA-[4'-phosphopantetheine] in 100 mM Tris-HCl, pH 7.8, at 30°C
    Pseudomonas aeruginosa 20 CoA-[4'-phosphopantetheine] in 100 mM Tris-HCl, pH 7.8, at 30°C
  • Temperature

    There are no reaction parameters information for this Enzyme.

  • pH
    Organism pH Range Comment
    Bacillus subtilis 4.5 - 8.5 less than 20% of maximum activity at both pH 5.0 and 7.0, 50% of activity maximum at pH 5.5 and pH 6.8
    Pseudomonas aeruginosa 5 - 7 pH 5: less than 27% of maximal activity, pH 7: less than 62% of maximal activity, activity with apo-[acyl-carrier protein]
    Escherichia coli 6 - 11 about 20% of activity maximum at pH 6.5, about 30% of activity maximum at pH 11.0
    Spinacia oleracea 7 - 8.8 half maximal activity at pH 7.4

Associated Proteins

Protein name Organism
Probable holo-[acyl-carrier-protein] synthase 2 Escherichia coli O157:H7
4'-phosphopantetheinyl transferase Npt Nocardia iowensis
Mitochondrial holo-[acyl-carrier-protein] synthase Baker's yeast
4'-phosphopantetheinyl transferase Svp Streptomyces mobaraensis
4'-phosphopantetheinyl transferase pptA Naked brimcap