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Information on EC 2.5.1.94 - adenosyl-chloride synthase
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EC Tree
2.5.1.94 adenosyl-chloride synthaseIUBMB Comments
This enzyme, isolated from the marine bacterium Salinispora tropica, catalyses an early step in the pathway leading to biosynthesis of the proteosome inhibitor salinosporamide A. The enzyme is very similar to EC 2.5.1.63, adenosyl-fluoride synthase, but does not accept fluoride.
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Word Map
- 2.5.1.94
-
chlorinate
-
halogen
-
fluorinase
- polyketide
- halogenase
- tropica
-
salinispora
- halide
- cattleya
-
salinosporamide
-
fluorination
- synthesis
-
flavin-dependent
- cl
- fluoride
-
congener
-
desolvation
-
chemoenzymatic
-
non-ribosomal
- flavin
-
fad-dependent
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
chlorinase, sam-dependent chlorinase, s-adenosyl-l-methionine-dependent chlorinase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5'-chloro-5'-deoxyadenosine synthase
-
-
-
-
AclH
chlorinase
Cla1
ClA2
SalL
SAM-dependent chlorinase
chlorinase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + chloride = 5-deoxy-5-chloroadenosine + L-methionine
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PATHWAY SOURCE
PATHWAYS
-
-
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:chloride adenosyltransferase
This enzyme, isolated from the marine bacterium Salinispora tropica, catalyses an early step in the pathway leading to biosynthesis of the proteosome inhibitor salinosporamide A. The enzyme is very similar to EC 2.5.1.63, adenosyl-fluoride synthase, but does not accept fluoride.
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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
2'-deoxy-2-ethynyladenosyl-L-methionine + fluoride
2'-deoxy-2-ethynyl-5'-fluoroadenosine + L-methionine
2'-deoxyadenosyl-L-methionine + fluoride
2'-deoxy-5'-fluoroadenosine + L-methionine
-
-
-
r
5-deoxy-5'-bromoadenosine + fluoride
5-deoxy-5'-fluoroadenosine + bromide
-
-
-
r
5-deoxy-5'-iodoadenosine + fluoride
5-deoxy-5'-fluoroadenosine + iodide
-
-
-
r
5-deoxy-5-chloroadenosine + S-(2-amino-2-carboxylethyl)-L-homocysteine
?
-
-
-
-
?
5-deoxy-5-chloroadenosine + S-(2-amino-2-oxoethyl)-L-homocysteine
?
-
-
-
-
?
S-adenosyl-L-methionine + bromide
5'-deoxy-5'-bromoadenosine + L-methionine
the enzyme also accepts bromide as substrate (with 90% relative activity compared to chloride) but the brominase activity is probably not biologically relevant in this marine bacterium
-
-
r
S-adenosyl-L-methionine + fluoride
5'-deoxy-5'-fluoroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + iodide
5'-deoxy-5'-iodoadenosine + L-methionine
the enzyme also accepts iodide as substrate (with 33% relative activity compared to chloride) but the iodinase activity is probably not biologically relevant in this marine bacterium
-
-
r
2'-deoxy-2-ethynyladenosyl-L-methionine + fluoride
2'-deoxy-2-ethynyl-5'-fluoroadenosine + L-methionine
-
-
-
-
r
2'-deoxy-2-ethynyladenosyl-L-methionine + fluoride
2'-deoxy-2-ethynyl-5'-fluoroadenosine + L-methionine
-
-
-
-
r
2'-deoxy-2-ethynyladenosyl-L-methionine + fluoride
2'-deoxy-2-ethynyl-5'-fluoroadenosine + L-methionine
-
-
-
-
r
5-deoxy-5'-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
r
5-deoxy-5'-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
-
r
5-deoxy-5'-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
r
5-deoxy-5'-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
-
r
5-deoxy-5'-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
-
r
5-deoxy-5-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
-
r
5-deoxy-5-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
most efficient reaction
-
-
r
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
?
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
?
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
?
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
chlorinase catalyzes chloride ion SN2 substitution at the C5' of S-adenosyl-L-methionine to generate 5'-deoxy-5'-chloroadenosine
-
-
?
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5-chloroadenosine + L-methionine
-
-
-
-
r
additional information
?
-
-
although this enzyme utilises bromide and even iodide it does not fluorinate
-
-
?
additional information
?
-
-
chlorinase does not accept fluoride ion as a substrate
-
-
?
additional information
?
-
the enzyme does not accept fluoride and 5-deoxy-5'-fluoroadenosine as substrates
-
-
?
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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
S-adenosyl-L-methionine + chloride
5'-deoxy-5'-chloroadenosine + L-methionine
-
-
-
-
r
5-deoxy-5-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
-
-
-
r
5-deoxy-5-chloroadenosine + L-methionine
S-adenosyl-L-methionine + chloride
-
most efficient reaction
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5-chloroadenosine + L-methionine
-
-
-
-
r
S-adenosyl-L-methionine + chloride
5-deoxy-5-chloroadenosine + L-methionine
-
-
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0002
5'-chloro-5'-deoxyadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0046
5'-deoxy-5'-iodoadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0097
5-deoxy-5'-bromoadenosine
37°C, direct displacement reaction in the absence of L-methionine or S-adenosyl-L-methionine, pH not specified in the publication
0.0095
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
0.014
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
0.001
S-adenosyl-L-methionine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0025
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
0.0157
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
5'-chloro-5'-deoxyadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.83
5'-deoxy-5'-iodoadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0003
5-deoxy-5'-bromoadenosine
37°C, direct displacement reaction in the absence of L-methionine or S-adenosyl-L-methionine, pH not specified in the publication
0.2
L-methionine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.208
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
0.248
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
0.011
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
0.015
S-adenosyl-L-methionine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.078
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1000
5'-chloro-5'-deoxyadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
181.1
5'-deoxy-5'-iodoadenosine
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.035
5-deoxy-5'-bromoadenosine
37°C, direct displacement reaction in the absence of L-methionine or S-adenosyl-L-methionine, pH not specified in the publication
0.0000883
bromide
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0003
chloride
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.0000192
Iodide
in 50 mM phosphate buffer (pH 7.9) at 37°C
0.077
L-methionine
in 50 mM phosphate buffer (pH 7.9) at 37°C
14.89
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
26.29
5-deoxy-5'-chloroadenosine
-
pH not specified in the publication, temperature not specified in the publication
4.502
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
4.968
S-adenosyl-L-methionine
-
pH not specified in the publication, temperature not specified in the publication
15
S-adenosyl-L-methionine
in 50 mM phosphate buffer (pH 7.9) at 37°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme, catalyzes both the reaction of fluorinase EC 2.5.1.63 and chlorinase Ec 2.5.1.94
UniProt
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
a chlorinase knockout mutated strain of Salinispora tropica is able to biosynthesis the fluorinated analogue of salinosporamide A, when the medium was supplemented with 5-deoxy-5-fluoroadenosine
metabolism
physiological function
metabolism
-
the enzyme catalyzes chlorination, the last step in the aspirochlorine pathway, modeling of the aspirochlorine biosynthesis involving an unusual Phe to Gly conversion, overview
metabolism
-
the enzyme is responsible for salinosporamide-A biosynthesis
metabolism
-
the enzyme catalyzes chlorination, the last step in the aspirochlorine pathway, modeling of the aspirochlorine biosynthesis involving an unusual Phe to Gly conversion, overview
-
physiological function
SalL functions in an orthogonal manner to biological chlorination reactions to initiate the biosynthesis of a new halogenated polyketide synthase building block
physiological function
-
key role of AclH as a chlorinase in the aspirochlorine biosynthesis. Aspirochlorine, or antibiotic A30641, is an epidithiodiketopiperazine toxin distinctive antifungal properties due to selective inhibition of protein biosynthesis produced from Aspergillus oryzae
physiological function
-
key role of AclH as a chlorinase in the aspirochlorine biosynthesis. Aspirochlorine, or antibiotic A30641, is an epidithiodiketopiperazine toxin distinctive antifungal properties due to selective inhibition of protein biosynthesis produced from Aspergillus oryzae
-
Show AA Sequence and Transmembrane Helices (260 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
3 * 30000, in solution as determined by sedimentation velocity studies
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotrimer
homotrimer
3 * 30000, in solution as determined by sedimentation velocity studies
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 28% (w/v) PEG 3350, 0.3 M KCl, 2 mM dithiothreitol, 0.1 M MOPSO, pH 7.0
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G131S
the mutation leads to the complete loss of all SalL halogenase activities and the inability to crystallize SalL
W129F
the mutant shows 52% chlorinase activity, 76% brominase activity, and 3% iodidase activity compared to the wild type enzyme
Y70T
the mutation results in a two-orders-of-magnitude reduction of SalL activity, the mutant shows 0.07% chlorinase activity, 0.1% brominase activity, and 0.4% iodidase activity compared to the wild type enzyme
Y70T/G131S
the mutant shows 0.3% chlorinase activity, 0.5% brominase activity, and no iodidase activity compared to the wild type enzyme
additional information
additional information
-
construction of an aclH deletion mutant of Aspergillus oryzae RIB40 strain, that is inactive with 3-chloro-L-tyrosine and 3-chloro-DL-phenylalanine. The DaclH mutant culture accumulates dechloroaspirochlorine. Complementation by ectopic integration of aclH in the DaclH mutant restores aspirochlorine production
additional information
-
construction of an aclH deletion mutant of Aspergillus oryzae RIB40 strain, that is inactive with 3-chloro-L-tyrosine and 3-chloro-DL-phenylalanine. The DaclH mutant culture accumulates dechloroaspirochlorine. Complementation by ectopic integration of aclH in the DaclH mutant restores aspirochlorine production
-
additional information
-
gene replacement of gene salL from Salinispora tropica by gene flA, EC 2.5.1.63, encoding fluorinase from Streptomaces cattleya, the recombinant fluorinase is functional in Salinispora tropica
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
gene aclH, DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis
-
gene salL, the gene is located in the middle of this salinosporamide A cluster
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
synthesis
-
deveopment of a coupled chlorinase-fluorinase system for rapid transhalogenation. The chlorinase shares a substrate tolerance with the fluorinase, enabling these two enzymes to cooperatively produce 5'-fluorodeoxy-2-ethynyladenosine in up to 91.6% yield in 1 h
synthesis
-
deveopment of a coupled chlorinase-fluorinase system for rapid transhalogenation. The chlorinase shares a substrate tolerance with the fluorinase, enabling these two enzymes to cooperatively produce 5'-fluorodeoxy-2-ethynyladenosine in up to 91.6% yield in 1 h
synthesis
-
deveopment of a coupled chlorinase-fluorinase system for rapid transhalogenation. The chlorinase shares a substrate tolerance with the fluorinase, enabling these two enzymes to cooperatively produce 5'-fluorodeoxy-2-ethynyladenosine in up to 91.6% yield in 1 h
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Deng, H.; McMahon, S.A.; Eustaquio, A.S.; Moore, B.S.; Naismith, J.H.; O'Hagan, D.
Mechanistic insights into water activation in SAM hydroxide adenosyltransferase (duf-62)
Chembiochem
10
2455-2459
2009
Salinispora tropica
brenda
Deng, H.; O'Hagan, D.
The fluorinase, the chlorinase and the duf-62 enzymes
Curr. Opin. Chem. Biol.
12
582-592
2008
Salinispora tropica
brenda
Deng, H.; Cobb, S.L.; McEwan, A.R.; McGlinchey, R.P.; Naismith, J.H.; OHagan, D.; Robinson, D.A.; Spencer, J.B.
The fluorinase from Streptomyces cattleya is also a chlorinase
Angew. Chem.
45
759-762
2006
Streptomyces cattleya
brenda
Eustaquio, A.S.; Pojer, F.; Noel, J.P.; Moore, B.S.
Discovery and characterization of a marine bacterial SAM-dependent chlorinase
Nat. Chem. Biol.
4
69-74
2008
Salinispora tropica CNB-440 (A4X3Q0)
brenda
Eustaquio, A.S.; McGlinchey, R.P.; Liu, Y.; Hazzard, C.; Beer, L.L.; Florova, G.; Alhamadsheh, M.M.; Lechner, A.; Kale, A.J.; Kobayashi, Y.; Reynolds, K.A.; Moore, B.S.
Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine
Proc. Natl. Acad. Sci. USA
106
12295-12300
2009
Salinispora tropica
brenda
Chankhamjon, P.; Boettger-Schmidt, D.; Scherlach, K.; Urbansky, B.; Lackner, G.; Kalb, D.; Dahse, H.M.; Hoffmeister, D.; Hertweck, C.
Biosynthesis of the halogenated mycotoxin aspirochlorine in koji mold involves a cryptic amino acid conversion
Angew. Chem. Int. Ed. Engl.
53
13409-13413
2014
Aspergillus oryzae, Aspergillus oryzae RIB 40
brenda
O'Hagan, D.; Deng, H.
Enzymatic fluorination and biotechnological developments of the fluorinase
Chem. Rev.
115
634-649
2015
Salinispora tropica
brenda
Sun, H.; Zhao, H.; Ang, E.
A coupled chlorinase-fluorinase system with a high efficiency of trans-halogenation and a shared substrate tolerance
Chem. Commun. (Camb.)
54
9458-9461
2018
uncultured bacterium, Streptomyces albulus, Umezawaea tangerina, Umezawaea tangerina NRRL B-24463
brenda
Thapa, H.R.; Lail, A.J.; Garg, N.; Agarwal, V.
Chemoenzymatic synthesis of starting materials and characterization of halogenases requiring acyl carrier protein-tethered substrates
Methods Enzymol.
604
333-366
2018
Salinispora tropica
brenda
Lowe, P.T.; Cobb, S.L.; OHagan, D.
An enzymatic Finkelstein reaction fluorinase catalyses direct halogen exchange
Org. Biomol. Chem.
17
7493-7496
2019
Streptomyces cattleya (Q70GK9)
brenda
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