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Information on EC 2.7.8.7 - holo-[acyl-carrier-protein] synthase and Organism(s) Escherichia coli and UniProt Accession P24224
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2.7.8.7 holo-[acyl-carrier-protein] synthaseIUBMB Comments
Requires Mg2+. All polyketide synthases, fatty-acid synthases and non-ribosomal peptide synthases require post-translational modification of their constituent acyl-carrier-protein (ACP) domains to become catalytically active. The inactive apo-proteins are converted into their active holo-forms by transfer of the 4'-phosphopantetheinyl moiety of CoA to the sidechain hydroxy group of a conserved serine residue in each ACP domain . The enzyme from human can activate both the ACP domain of the human cytosolic multifunctional fatty-acid synthase system (EC 2.3.1.85) and that associated with human mitochondria as well as peptidyl-carrier and acyl-carrier-proteins from prokaryotes . Removal of the 4-phosphopantetheinyl moiety from holo-ACP is carried out by EC 3.1.4.14, [acyl-carrier-protein] phosphodiesterase.
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Word Map
- 2.7.8.7
-
phosphopantetheinylation
- polyketide
-
4\'-phosphopantetheinyl
-
nonribosomal
- synthetases
-
peptidyl
-
siderophore
-
lipopeptide
-
nrpss
- apo-acp
- enterobactin
-
holo-forms
-
biosurfactant
-
fengycin
-
indigoidine
- biotechnology
- alpha-aminoadipate
- analysis
- drug development
- molecular biology
- medicine
- synthesis
-
iturins
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
+
=
+
+
an apo-[acyl-carrier protein]
=
+
Synonyms
pptase, phosphopantetheinyl transferase, surfactin synthetase, 4'-phosphopantetheinyl transferase, mtppt, type ii fatty acid synthase system, sfp-type pptase, schppt, holo-acyl carrier protein synthase, sfp-pptase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
4'-phosphopantetheinyl transferase
acyl carrier protein holoprotein (holo-ACP) synthetase
-
-
-
-
acyl carrier protein synthetase
-
-
-
-
coenzyme A:fatty acid synthetase apoenzyme 4'-phosphopantetheine transferase
-
-
-
-
EntD
holo-ACP synthase
-
-
-
-
holo-ACP synthetase
-
-
-
-
holosynthase
-
-
-
-
PPTase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
substituted phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
CoA-[4'-phosphopantetheine]:apo-[acyl-carrier protein] 4'-pantetheinephosphotransferase
Requires Mg2+. All polyketide synthases, fatty-acid synthases and non-ribosomal peptide synthases require post-translational modification of their constituent acyl-carrier-protein (ACP) domains to become catalytically active. The inactive apo-proteins are converted into their active holo-forms by transfer of the 4'-phosphopantetheinyl moiety of CoA to the sidechain hydroxy group of a conserved serine residue in each ACP domain [3]. The enzyme from human can activate both the ACP domain of the human cytosolic multifunctional fatty-acid synthase system (EC 2.3.1.85) and that associated with human mitochondria as well as peptidyl-carrier and acyl-carrier-proteins from prokaryotes [6]. Removal of the 4-phosphopantetheinyl moiety from holo-ACP is carried out by EC 3.1.4.14, [acyl-carrier-protein] phosphodiesterase.
CAS REGISTRY NUMBER
COMMENTARY
37278-30-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-hydroxybutanoyl-CoA + apo-[acyl-carrier protein]
CoA + 3-hydroxybutanoyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
acetoacetyl-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
?
acetoacetyl-CoA + apo-[acyl-carrier protein]
CoA + acetoacetyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
acetyl-CoA + apo-[acyl-carrier protein]
CoA + acetyl-[acyl-carrier protein]
-
-
-
?
butanoyl-CoA + apo-[acyl-carrier protein]
CoA + butanoyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
butyryl-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
?
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
crotonyl-CoA + apo-[acyl-carrier protein]
CoA + crotonyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
dodecanoyl-CoA + apo-[acyl-carrier protein]
CoA + dodecanoyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
lauroyl-CoA + apo-[acyl-carrier protein]
CoA + lauroyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
malonyl-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
?
malonyl-CoA + apo-[acyl-carrier protein]
CoA + malonyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
myristoyl-CoA + apo-[acyl-carrier protein]
CoA + myristoyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
palmitoyl-CoA + apo-[acyl-carrier protein]
CoA + palmitoyl-[acyl-carrier protein]
substrate Plasmodium falciparum apo-[acyl-carrier protein]
-
-
?
acetonyldethio-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
-
r
biotin-CoA + DSLEFIASKLA
D-(biotinyl-4'-phosphopantetheinyl)SLEFIASKLA + ?
-
-
-
-
?
biotin-CoA + GDSLDMLEWSLM
GD-(biotinyl-4'-phosphopantetheinyl)SLDMLEWSLM + ?
-
-
-
-
?
biotin-CoA + GDSLSWLLRCLN
GD-(biotinyl-4'-phosphopantetheinyl)SLSWLLRCLN + ?
-
-
-
-
?
biotin-CoA + GDSLSWLLRLLN
GD-(biotinyl-4'-phosphopantetheinyl)SLSWLLRLLN + ?
-
-
-
-
?
biotin-CoA + GDSLSWLLRSLN
GD-(biotinyl-4'-[N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}-3-(2,5-dioxopyrrolidin-1-yl)propanamide]phosphopantetheinyl)SLSWLLRSLN + ?
-
-
-
-
?
biotin-CoA + GDSLSWLVRCLN
GD-(biotinyl-4'-phosphopantetheinyl)SLSWLVRCLN + ?
-
-
-
-
?
biotin-CoA + GDSLSWLVRLLN
GD-(biotinyl-4'-phosphopantetheinyl)SLSWLVRLLN + ?
-
-
-
-
?
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
CoA + apo-[Streptomyces sp. frenolicin-acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[Streptomyces sp. frenolicin-acyl-carrier protein]
-
-
-
-
r
CoA + apo-[Streptomyces sp. granaticin-acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[Streptomyces sp. granaticin-acyl-carrier protein]
-
-
-
-
r
CoA + apo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
-
-
-
-
r
CoA + apo-[Streptomyces sp. tetracenomycin-acyl-carrier protein(His6)]
adenosine 3',5'-bisphosphate + holo-[Streptomyces sp. tetracenomycin-acyl-carrier protein(His6)]
-
-
-
-
r
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
CoA-[4'-phosphopantetheine] + apo-[BpsA protein]
adenosine 3',5'-bisphosphate + holo-[BpsA protein]
-
-
-
-
?
desulfo-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
-
r
desulfoCoA + apo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
? + holo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
-
-
-
-
r
homocysteamine-CoA + apo-[acyl-carrier protein]
? + holo-[acyl-carrier protein]
-
-
-
-
r
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
the enzyme AcpS is active with type II FAS ACP, AcpP, but the enzyme accepts not only bacterial AcpP but a variety of CPs from type II elongating systems including Lactobacillus casei D-alanyl carrier protein, Rhizobia protein NodF and Streptomyces ACPs involved in frenolicin, granaticin, oxytetracycline and tetracenomycin polyketide biosynthesis
-
-
?
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
transfers 4'-phosphopantetheine from reduced coenzyme A to acyl carrier proteon apoprotein
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
Dcp from Lactobacillus casei, NodF from Rhizobium leguminosarum and several polyketide synthase ACPs from Streptomyces sp. also serves as substrates
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
Streptomycess sp. acyl carrier proteins and coenzyme A analogs also serves as substrates for holo-ACP synthase in vitro
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
ACP serves as cofactor in the biosynthesis of fatty acids and the biosynthesis of complex lipids
-
r
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases. Sfp is the PPTase necessary for installing PPant on the PCP of surfactin synthase
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
the carrier protein of Colibactin is phosphopantetheinylated by the family II PPTase ClbA
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
the carrier protein of the enterobactin synthase complex, EntF, is phosphopantetheinylated by the family II PPTase EntD. In vitro EntD seems to modify apo-AcpP from Escherichia coli, albeit at a very slow rate
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
the enzyme Sfp is active with surfactin synthase peptidyl carrier protein. Sfp shows highly permissive catalytic activity towards CPs using not only CoA but CoA-like substrates
-
-
?
additional information
?
-
besides enterobactin and colibactin, some Escherichia coli strains also produce yersiniabactin. Yersiniabactin is encoded by the high-pathogenicity island and in contrast to Yersinia pestis (in Yersinia pestis YbtD is the dedicated PPTase) no PPTase is found in the Escherichia coli genome that seems to activate this synthase
-
-
?
additional information
?
-
besides enterobactin and colibactin, some Escherichia coli strains also produce yersiniabactin. Yersiniabactin is encoded by the high-pathogenicity island and in contrast to Yersinia pestis (in Yersinia pestis YbtD is the dedicated PPTase) no PPTase is found in the Escherichia coli genome that seems to activate this synthase
-
-
?
additional information
?
-
besides enterobactin and colibactin, some Escherichia coli strains also produce yersiniabactin. Yersiniabactin is encoded by the high-pathogenicity island and in contrast to Yersinia pestis (in Yersinia pestis YbtD is the dedicated PPTase) no PPTase is found in the Escherichia coli genome that seems to activate this synthase
-
-
?
additional information
?
-
besides enterobactin and colibactin, some Escherichia coli strains also produce yersiniabactin. Yersiniabactin is encoded by the high-pathogenicity island and in contrast to Yersinia pestis (in Yersinia pestis YbtD is the dedicated PPTase) no PPTase is found in the Escherichia coli genome that seems to activate this synthase
-
-
?
additional information
?
-
carrier proteins from type I elongating systems are not substrates for AcpS. Inability of Escherichia coli AcpS to install a PPant arm on apo-EntF, the bacterial enterobactin synthase, or apo-TycA, the Bacillus brevis tyrocidine synthase
-
-
?
additional information
?
-
carrier proteins from type I elongating systems are not substrates for AcpS. Inability of Escherichia coli AcpS to install a PPant arm on apo-EntF, the bacterial enterobactin synthase, or apo-TycA, the Bacillus brevis tyrocidine synthase
-
-
?
additional information
?
-
carrier proteins from type I elongating systems are not substrates for AcpS. Inability of Escherichia coli AcpS to install a PPant arm on apo-EntF, the bacterial enterobactin synthase, or apo-TycA, the Bacillus brevis tyrocidine synthase
-
-
?
additional information
?
-
carrier proteins from type I elongating systems are not substrates for AcpS. Inability of Escherichia coli AcpS to install a PPant arm on apo-EntF, the bacterial enterobactin synthase, or apo-TycA, the Bacillus brevis tyrocidine synthase
-
-
?
additional information
?
-
ACPS accepts very efficiently acyl-CoAs with chain lengths up to C16, and with decreasing activity also longer chains (C18 to C20)
-
-
-
additional information
?
-
-
mutant ACP in which the target serine 36 has been mutated to a threonine residue is an inactive substrate for phosphopantetheinylation
-
-
?
additional information
?
-
-
specificity of the holo-ACP synthetase is not examined in detail, only CoA is the donor of the 4'-phosphopantetheine moiety, dephospho-CoA is essentially inactive
-
-
?
additional information
?
-
-
specificity of the holo-ACP synthetase is not examined in detail, only CoA is the donor of the 4'-phosphopantetheine moiety, dephospho-CoA is essentially inactive
-
-
?
additional information
?
-
-
isoform AcpT modifies two carrier proteins encoded in O-island 138, a cluster of fatty acid biosynthesis-like genes
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases
-
-
?
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
additional information
?
-
-
isoform AcpT modifies two carrier proteins encoded in O-island 138, a cluster of fatty acid biosynthesis-like genes
-
-
?
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
-
-
r
CoA + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
ACP serves as cofactor in the biosynthesis of fatty acids and the biosynthesis of complex lipids
-
r
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases
-
-
?
CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases. Sfp is the PPTase necessary for installing PPant on the PCP of surfactin synthase
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
additional information
additional information
-
Ca2+, Fe2+, Co2+ and Zn2+ are ineffective, inhibitory or both, at intermediate and high concentrations
additional information
-
CuSO4, CdCl2 and CrCl2 does not stimulate the reaction at any ceoncentration, trivalent metal cations such as FeCl3 or AlCl3 are ineffective
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
apo-acyl-carrier protein
-
mutant ACP in which the target serine 36 has been mutated to a threonine residue is an inhibitor as well as an inactive substrate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
apo-[Streptomyces sp. frenolicin-acyl-carrier protein]
-
pH 7.0, 37°C, Escherichia coli acyl carrier protein
0.005
apo-[Streptomyces sp. granaticin-acyl-carrier protein]
-
pH 7.0, 37°C, Escherichia coli acyl carrier protein
0.039
apo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
-
pH 7.0, 37°C, Escherichia coli acyl carrier protein
0.022
apo-[Streptomyces sp. tetracenomycin-acyl-carrier protein(His6)]
-
pH 7.0, 37°C, Escherichia coli acyl carrier protein
additional information
additional information
holo-ACPP binds the enzyme with greater affinity than the substrate, apo-ACPP, and with negative cooperativity. Cooperativity is not observed for apo-ACPP
-
0.002
apo-acyl-carrier protein
-
pH 7.0, 37°C, Escherichia coli acyl carrier protein
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.317
apo-[Streptomyces sp. frenolicin-acyl-carrier protein]
-
pH 7.0, 37°C, E. coli ACP
0.5
apo-[Streptomyces sp. granaticin-acyl-carrier protein]
-
pH 7.0, 37°C, E. coli ACP
0.167
apo-[Streptomyces sp. oxytetracycline-acyl-carrier protein]
-
pH 7.0, 37°C, E. coli ACP
0.09
apo-[Streptomyces sp. tetracenomycin-acyl-carrier protein(His6)]
-
pH 7.0, 37°C, E. coli ACP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.054
apo-[Streptomyces sp. frenolicin-acyl-carrier protein]
-
pH 7.0, 37°C, E. coli ACP
0.0006
apo-[Streptomyces sp. granaticin-acyl-carrier protein]
-
pH 7.0, 37°C, E. coli ACP
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.32
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 11
-
about 20% of activity maximum at pH 6.5, about 30% of activity maximum at pH 11.0
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
9.25
-
calculated from molar extinction coefficient by the method of Gill and von Hippel
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
phosphopantetheinyl transferases (PPTases) are essential for cell viability across all three domains of life: bacteria, archaea and eukaryota. Holo-ACP synthase (AcpS) is the archetypical enzyme of the first family of PPTases recognized. Surfactin phosphopantetheinyl transferase (Sfp) represents the second family of PPTases. The third family of PPTases are translationally fused C-terminal transferases residing in the megasynthases as one of several catalytic domains acting in type I yeast and fungal FAS megasynthases. This third family of PPTases post-translationally modify apo-ACPs prior to assembly of the megasynthases
malfunction
overproduction of AcpS cannot compensate the absence of EntD. Conversely, overexpressing entD on an inducible plasmid cannot complement the absence of acpS
physiological function
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases. Mechanistically distinct classes of enzymes have been identified that require PPant arms for biosynthetic catalysis. These include enzymes involved in the biosynthesis of lipid A, D-alanyllipoteichoic acid, lipo-chitin nodulation factor, beta-alanine-dopamine conjugates, carboxylic acid reductions, and dehydrogenation of alpha-aminoadipate semialdehyde (lysine biosynthesis) and 10-formyl-tetrahydrofolate. Essential enzymatic role of PPTases in general fatty acid biosynthesis. AcpSs are primarily used for post-translational modification and activation of the carrier proteins of FASs (primary metabolism) across a diversity of organisms making them the most commonly found PPTase
evolution
malfunction
gene entD knockout in Escherichia coli strain AN90-60 results in a strain that does not produce enterobactin. Overproduction of AcpS cannot compensate the absence of EntD. Conversely, overexpressing entD on an inducible plasmid cannot complement the absence of acpS. The pobA gene from Burkholderia cenocepacia is shown to efficiently complement an Escherichia coli entD mutant
metabolism
-
the enzyme is essential for activation of non-ribosomal peptide synthetase and polyketide synthase enzymes
physiological function
evolution
phosphopantetheinyl transferases (PPTases) are essential for cell viability across all three domains of life: bacteria, archaea and eukaryota. Holo-ACP synthase (AcpS) is the archetypical enzyme of the first family of PPTases recognized. Surfactin phosphopantetheinyl transferase (Sfp) represents the second family of PPTases. The third family of PPTases are translationally fused C-terminal transferases residing in the megasynthases as one of several catalytic domains acting in type I yeast and fungal FAS megasynthases. This third family of PPTases post-translationally modify apo-ACPs prior to assembly of the megasynthases. The second family enzymes contain two highly conserved regions, called ppt-1 and ppt-3, generalized as the bipartite sequence, (I/V/L)G(I/V/L/T)D(I/V/L/A)(x)n(F/W)(A/S/T/C)xKE(S/A)h(h/S)K(A/G), where x are chemically disparate amino acids, n is 4248 aa for AcpS (family I) and 3841 aa for Sfp-type (family II) PPTases, and h is an amino acid with a hydrophobic side chain
evolution
phosphopantetheinyl transferases (PPTases) are essential for cell viability across all three domains of life: bacteria, archaea and eukaryota. Holo-ACP synthase (AcpS) is the archetypical enzyme of the first family of PPTases recognized. Surfactin phosphopantetheinyl transferase (Sfp) represents the second family of PPTases. The third family of PPTases are translationally fused C-terminal transferases residing in the megasynthases as one of several catalytic domains acting in type I yeast and fungal FAS megasynthases. This third family of PPTases post-translationally modify apo-ACPs prior to assembly of the megasynthases. The second family enzymes contain two highly conserved regions, called ppt-1 and ppt-3, generalized as the bipartite sequence, (I/V/L)G(I/V/L/T)D(I/V/L/A)(x)n(F/W)(A/S/T/C)xKE(S/A)h(h/S)K(A/G), where x are chemically disparate amino acids, n is 4248 aa for AcpS (family I) and 3841 aa for Sfp-type (family II) PPTases, and h is an amino acid with a hydrophobic side chain. The toxin found in a hybrid PKS-NRPS cluster, (also known as PKS island) produces colibactin. Within this cluster, clbA is identified as a PPTase
physiological function
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases. Mechanistically distinct classes of enzymes have been identified that require PPant arms for biosynthetic catalysis. These include enzymes involved in the biosynthesis of lipid A, D-alanyllipoteichoic acid, lipo-chitin nodulation factor, beta-alanine-dopamine conjugates, carboxylic acid reductions, and dehydrogenation of alpha-aminoadipate semialdehyde (lysine biosynthesis) and 10-formyl-tetrahydrofolate. Essential enzymatic role of PPTases in general fatty acid biosynthesis
physiological function
PPTases posttranslationally modify modular and iterative synthases acting in a processive fashion, namely fatty acid synthases, polyketide synthases, and non-ribosomal peptide syntethases. The central component of these chain elongating synthases is non-catalytic and either a translationally linked domain of a larger polypeptide chain or an independently translated protein. Regardless, this protein component is referred to as a carrier protein, or alternatively a thiolation domain. The CP tethers the growing intermediates on a 4'-phosphopantetheine (PPant) arm of 20 A through a reactive thioester linkage. PPants are thought of as prosthetic arms on which all substrates and intermediates of these pathways are covalently yet transiently held during the orderly progression of enzymatic modifications to the extending chain. PPTases mediate the transfer and covalent attachment of PPant arms from coenzyme A (CoA) to conserved serine residues of the carrier protein domain through phosphoester bonds. These essential posttranslation protein modifications convert inactive apo-synthases to active holo-synthases. Mechanistically distinct classes of enzymes have been identified that require PPant arms for biosynthetic catalysis. These include enzymes involved in the biosynthesis of lipid A, D-alanyllipoteichoic acid, lipo-chitin nodulation factor, beta-alanine-dopamine conjugates, carboxylic acid reductions, and dehydrogenation of alpha-aminoadipate semialdehyde (lysine biosynthesis) and 10-formyl-tetrahydrofolate. The PPTase ClbA can activate both siderophore and genotoxin biosynthesis
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
18470
-
2 * 18470, calculated from molar extinction coefficient by the method of Gill and von Hippel
28000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotrimer
3 * 28000, AcpS has a quaternary structure with active sites shared across each homotypic interface
homodimer
homodimer
-
2 * 18470, calculated from molar extinction coefficient by the method of Gill and von Hippel
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structures of ACPS in unliganded and holo-ACPP-bound forms, to 2.05 A and 4.10 A resolution, respectively. ACPS binds three product holo-ACPP molecules to form a 3:3 hexamer. The binding interface is organized to arrange contacts between positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
isoform AcpT cannot functially replace isoform AcpS. However, in the absence of AcpS activity, isoform AcpT allows very slow growth
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
very unstable, markedly protected from inactivation by the presence of half-saturating concentrations of reduced CoA
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-196°C, stored in liquid nitrogen, enzyme maintains full activity for at least 1 year
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene acpP cloned and overproduced from recombinant Escherichia coli BL21(DE3)pDPJ
-
gene clbA, in family II PPTases, the genes encoding the PPTase often reside in close proximity to, or part of, a synthase operon
gene entD, in family II PPTases, the genes encoding the PPTase often reside in close proximity to, or part of, a synthase operon
gene sfp, in family II PPTases, the genes encoding the PPTase often reside in close proximity to, or part of, a synthase operon
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
enzyme can be utilized in an assay for apo-ACP in biological material
biotechnology
-
identification of short peptide tags of 12 residues as efficient substrate for site-specific protein labeling catalyzed by enzyme
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Prescott, D.J.; Vagelos, P.R.
Acyl carrier protein
Adv. Enzymol. Relat. Areas Mol. Biol.
36
269-311
1972
Saccharomyces cerevisiae, Clostridium kluyveri, Escherichia coli, Rattus norvegicus
Elovson, J.; Vagelos, P.R.
Acyl carrier protein. X. Acyl carrier protein synthetase
J. Biol. Chem.
243
3603-3611
1968
Escherichia coli, Escherichia coli B / ATCC 11303
Prescott, D.J.; Elovson, J.; Vagelos, P.R.
Acyl carrier protein synthetase
Methods Enzymol.
35B
95-101
1975
Escherichia coli, Escherichia coli B / ATCC 11303
-
Lambalot, R.H.; Walsh, C.T.
Cloning, overproduction, and characterization of the Escherichia coli holo-acyl carrier protein synthase
J. Biol. Chem.
270
24658-24661
1995
Escherichia coli
Gehring, A.M.; Lambalot, R.H.; Vogel, K.W.; Drueckhammer, D.G.; Walsh, C.T.
Ability of Streptomyces spp. acyl carrier proteins and coenzyme A analogs to serve as substrates in vitro for E. coli holo-ACP synthase
Chem. Biol.
4
17-24
1997
Escherichia coli
Lambalot, R.H.; Walsh, C.T.
Holo-[acyl-carrier-protein] synthase of Escherichia coli
Methods Enzymol.
279
254-262
1997
Escherichia coli
Flugel, R.S.; Hwangbo, Y.; Lambalot, R.H.; Cronan, J.E., Jr.; Walsh, C.T.
Holo-(acyl carrier protein) synthase and phosphopantetheinyl transfer in Escherichia coli
J. Biol. Chem.
275
959-968
2000
Escherichia coli, no activity in Escherichia coli, no activity in Escherichia coli MP4
Zhou, Z.; Cironi, P.; Lin, A.J.; Xu, Y.; Hrvatin, S.; Golan, D.E.; Silver, P.A.; Walsh, C.T.; Yin, J.
Genetically encoded short peptide tags for orthogonal protein labeling by Sfp and AcpS phosphopantetheinyl transferases
ACS Chem. Biol.
2
337-346
2007
Bacillus subtilis, Escherichia coli
McAllister, K.A.; Peery, R.B.; Zhao, G.
Acyl carrier protein synthases from Gram-negative, Gram-positive, and atypical bacterial species: Biochemical and structural properties and physiological implications
J. Bacteriol.
188
4737-4748
2006
Streptococcus pneumoniae, Mycoplasma pneumoniae, Escherichia coli (P24224)
De Lay, N.R.; Cronan, J.E.
A genome rearrangement has orphaned the Escherichia coli K-12 AcpT phosphopantetheinyl transferase from its cognate Escherichia coli O157:H7 substrates
Mol. Microbiol.
61
232-242
2006
Escherichia coli
Owen, J.G.; Robins, K.J.; Parachin, N.S.; Ackerley, D.F.
A functional screen for recovery of 4'-phosphopantetheinyl transferase and associated natural product biosynthesis genes from metagenome libraries
Environ. Microbiol.
14
1198-1209
2012
Escherichia coli
Beld, J.; Sonnenschein, E.C.; Vickery, C.R.; Noel, J.P.; Burkart, M.D.
The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life
Nat. Prod. Rep.
31
61-108
2014
Bacillus anthracis, Bacillus licheniformis, Bacillus subtilis (P39135), Bacillus subtilis 168 (P39135), Brevibacillus brevis, Burkholderia cenocepacia (Q27IP6), Burkholderia pseudomallei (Q63I03), Burkholderia pseudomallei K96243 (Q63I03), Escherichia coli (E2QFX9), Escherichia coli (P19925), Escherichia coli (P24224), Escherichia coli (Q0P7J0), Mycobacterium tuberculosis (P9WQD3), Mycobacterium tuberculosis H37Rv (P9WQD3), Pseudomonas aeruginosa (Q9I4H2), Pseudomonas aeruginosa DSM 22644 (Q9I4H2), Serratia marcescens (Q75PZ2), Serratia marcescens Db11 (Q75PZ2), Streptomyces coelicolor, Streptomyces coelicolor (O86785), Streptomyces coelicolor (O88029), Streptomyces coelicolor ATCC BAA-471 (O86785), Vibrio anguillarum (Q5DK20), Vibrio anguillarum ATCC 68554 (Q5DK20), Vibrio cholerae (Q9RCF2), Xanthomonas albilineans (D2U8G6), Xanthomonas albilineans GPE PC73 (D2U8G6), Yersinia pestis (Q74V64)
Lauciello, L.; Lack, G.; Scapozza, L.; Perozzo, R.
A high yield optimized method for the production of acylated ACPs enabling the analysis of enzymes involved in P. falciparum fatty acid biosynthesis
Biochem. Biophys. Rep.
8
310-317
2016
Escherichia coli (P24224)
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