Information on EC 2.5.1.106 - tryprostatin B synthase

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The expected taxonomic range for this enzyme is: Aspergillus fumigatus

EC NUMBER
COMMENTARY hide
2.5.1.106
-
RECOMMENDED NAME
GeneOntology No.
tryprostatin B synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
dimethylallyl diphosphate + brevianamide F = diphosphate + tryprostatin B
show the reaction diagram
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
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-
fumitremorgin C biosynthesis
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Staurosporine biosynthesis
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fumitremorgin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
dimethylallyl-diphosphate:brevianamide-F dimethylallyl-C-2-transferase
The enzyme from the fungus Aspergillus fumigatus can also prenylate other tryptophan-containing cyclic dipeptides. Prenylation occurs mainly at C-2 [1], but also at C-3 [2]. Involved in the biosynthetic pathways of several indole alkaloids such as tryprostatins, cyclotryprostatins, spirotryprostatins, fumitremorgins and verruculogen.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dimethylallyl diphosphate + (E)-4-(1H-indol-3-yl)but-3-en-2-one
diphosphate + (3E)-3-(1H-indol-3-ylmethylidene)-6-methylhept-5-en-2-one
show the reaction diagram
dimethylallyl diphosphate + 2-methylbrevianamide F
diphosphate + ?
show the reaction diagram
-
i.e. cyclo-L-2-methyltryptophan-L-proline
-
-
?
dimethylallyl diphosphate + 5-hydroxybrevianamide F
diphosphate + ?
show the reaction diagram
-
i.e. cyclo-L-5-hydroxytryptophan-L-proline
-
-
?
dimethylallyl diphosphate + brevianamide F
diphosphate + (2S,3aR,8aR)-3a-(2-methylbut-3-en-2-yl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid
show the reaction diagram
dimethylallyl diphosphate + brevianamide F
diphosphate + (5aS,6aR,11aR,13aS)-6a-(3-methylbut-2-en-1-yl)-2,3,6,6a,11,11a-hexahydro-1H-pyrrolo[1'',2'':4',5']pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-5,13(5aH,13aH)-dione
show the reaction diagram
dimethylallyl diphosphate + brevianamide F
diphosphate + tryprostatin B
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-D-Ala)
diphosphate + cyclo-(D-2-dimethylallyl-Trp-D-Ala)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-D-Pro)
diphosphate + cyclo-(2-dimethylallyl-Trp-D-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-D-Pro)
diphosphate + cyclo-(D-2-dimethylallyl-Trp-D-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-L-Ala)
diphosphate + cyclo-(D-2-dimethylallyl-Trp-L-Ala)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-L-Pro)
diphosphate + cyclo-(2-dimethylallyl-D-Trp-L-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-L-Pro)
diphosphate + cyclo-(2-dimethylallyl-Trp-L-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(D-Trp-L-Pro)
diphosphate + cyclo-(D-2-dimethylallyl-Trp-L-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-D-Ala)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-D-Ala)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-D-Pro)
diphosphate + cyclo-(2-dimethylallyl-Trp-D-Pro)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-D-Pro)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-D-Pro)
show the reaction diagram
product yield 75.7%
-
-
?
dimethylallyl diphosphate + cyclo-(L-Trp-Gly)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-Gly)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-Ala)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-L-Ala)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-His)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-L-His)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-Leu)
diphosphate + cyclo-(D-2-dimethylallyl-Trp-L-Leu)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-Phe)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-L-Phe)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-Pro)
diphosphate + cyclo-(2-dimethylallyl-Trp-L-Pro)
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + cyclo-(L-Trp-L-Trp)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-L-Trp)
show the reaction diagram
dimethylallyl diphosphate + cyclo-(L-Trp-L-Tyr)
diphosphate + cyclo-(L-2-dimethylallyl-Trp-L-Tyr)
show the reaction diagram
dimethylallyl diphosphate + cyclo-L-2-methyltryptophan-L-proline
diphosphate + (5aS,6aS,13aS)-6a-(3-methylbut-2-en-1-yl)-2,3,6,6a,11,11a-hexahydro-1H-pyrrolo[1'',2'':4',5']pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-5,13(5aH,13aH)-dione
show the reaction diagram
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i.e. 2-methylbrevianamide F
product is a normal prenylated hexahydropyrroloindole that contains a substituent at C-3 and has cyclized. An N-1 normal prenylated product is formed as minor product
-
?
dimethylallyl diphosphate + DL-4-methyl-tryptophan
diphosphate + DL-1-(3'-dimethylallyl)-4-methyl-tryptophan
show the reaction diagram
dimethylallyl diphosphate + DL-6-fluoro-tryptophan
diphosphate + DL-1-(3'-dimethylallyl)-6-fluoro-tryptophan
show the reaction diagram
dimethylallyl diphosphate + DL-6-methyl-tryptophan
diphosphate + DL-1-(3'-dimethylallyl)-6-methyl-tryptophan
show the reaction diagram
dimethylallyl diphosphate + DL-7-methyl-tryptophan
diphosphate + DL-1-(3'-dimethylallyl)-7-methyl-tryptophan
show the reaction diagram
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conversion rate 24.3%
-
?
dimethylallyl diphosphate + L-Nalpha-methyl-tryptophan
diphosphate + L-1-(3'-dimethylallyl)-Nalpha-methyl-tryptophan
show the reaction diagram
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-
conversion rate 11.1%
-
?
dimethylallyl diphosphate + L-tryptophan
diphosphate + (2S,3aR,8aR)-3a-(2-methylbut-3-en-2-yl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid
show the reaction diagram
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18% conversion after extended incubation, product is a hexahydropyrroloindole that results from reverse C-3 prenylation followed by ring closure
-
?
dimethylallyl diphosphate + L-tryptophan
diphosphate + ?
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + L-tryptophan
diphosphate + L-1-(3'-dimethylallyl)-tryptophan
show the reaction diagram
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conversion rate 37.8%
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?
dimethylallylphosphate + cyclo-L-5-hydroxytryptophan-L-proline
diphosphate + (3S,8aS)-3-[[5-hydroxy-4-(3-methylbut-2-en-1-yl)-2,3-dihydro-1H-indol-3-yl]methyl]hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
show the reaction diagram
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i.e. 5-hydroxybrevianamide F
product is formed by normal prenylation in C-4 position
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
dimethylallyl diphosphate + brevianamide F
diphosphate + tryprostatin B
show the reaction diagram
-
i.e. cyclo-L-Trp-L-Pro
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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at 2-5 mM, slight activation
Mg2+
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at 2-5 mM, slight activation. Inhibitory above 10 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Mg2+
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at 2-5 mM, slight activation. Inhibitory above 10 mM
Mn2+
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inhibitory above 5 mM
Zn2+
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inhibitory above 5 mM
additional information
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not inhibitory: EDTA up to 5 mM
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.88
(E)-4-(1H-indol-3-yl)but-3-en-2-one
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pH not specified in the publication, temperature not specified in the publication
0.055 - 0.16
brevianamide F
0.14 - 0.32
cyclo-(D-Trp-D-Pro)
0.14 - 0.39
cyclo-(D-Trp-L-Ala)
0.4 - 0.46
cyclo-(D-Trp-L-Pro)
0.41
cyclo-(L-Trp-D-Ala)
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pH 7.5, 37C, prenylation at C2
0.083 - 0.62
cyclo-(L-Trp-D-Pro)
0.69 - 0.77
cyclo-(L-Trp-Gly)
0.48 - 0.54
cyclo-(L-Trp-L-Ala)
0.45
cyclo-(L-Trp-L-His)
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pH 7.5, 37C, prenylation at C2
0.057 - 0.19
cyclo-(L-Trp-L-Pro)
-
0.27 - 0.37
cyclo-(L-Trp-L-Tyr)
0.074
dimethylallyl diphosphate
-
pH 7.5, 30C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.4
(E)-4-(1H-indol-3-yl)but-3-en-2-one
Aspergillus fumigatus
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pH not specified in the publication, temperature not specified in the publication
4.05 - 5.57
brevianamide F
0.25 - 1.39
cyclo-(D-Trp-D-Pro)
0.06 - 0.24
cyclo-(D-Trp-L-Ala)
0.21 - 0.41
cyclo-(D-Trp-L-Pro)
0.71
cyclo-(L-Trp-D-Ala)
Aspergillus fumigatus
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pH 7.5, 37C, prenylation at C2
0.18 - 0.32
cyclo-(L-Trp-D-Pro)
2.55 - 3.14
cyclo-(L-Trp-Gly)
0.13 - 1.47
cyclo-(L-Trp-L-Ala)
21.14
cyclo-(L-Trp-L-His)
Aspergillus fumigatus
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pH 7.5, 37C, prenylation at C2
1.36 - 8.9
cyclo-(L-Trp-L-Pro)
-
0.09 - 1.73
cyclo-(L-Trp-L-Tyr)
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
25.3
brevianamide F
Aspergillus fumigatus
-
pH 7.5, 37C, prenylation at C2
6395
0.78 - 4.9
cyclo-(D-Trp-D-Pro)
28944
0.43 - 0.61
cyclo-(D-Trp-L-Ala)
19738
0.53 - 0.89
cyclo-(D-Trp-L-Pro)
89343
1.73
cyclo-(L-Trp-D-Ala)
Aspergillus fumigatus
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pH 7.5, 37C, prenylation at C2
42426
0.52 - 2.2
cyclo-(L-Trp-D-Pro)
173321
3.69 - 4.08
cyclo-(L-Trp-Gly)
19735
0.27 - 2.72
cyclo-(L-Trp-L-Ala)
19737
4.76
cyclo-(L-Trp-L-His)
Aspergillus fumigatus
-
pH 7.5, 37C, prenylation at C2
42427
12 - 156
cyclo-(L-Trp-L-Pro)
214004
0.25 - 6.41
cyclo-(L-Trp-L-Tyr)
19736
PDB
SCOP
CATH
ORGANISM
UNIPROT
Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100)
Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
49000
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1 * 49000, SDS-PAGE, 1 * 53400, calculated
53400
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1 * 49000, SDS-PAGE, 1 * 53400, calculated
66000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structures of unliganded enzyme FtmPT1 to 2.5 A resolution as well as of a ternary complex of FtmPT1 bound to brevianamide F and an analogue of its isoprenoid substrate dimethylallyl diphosphate. FtmPT1 assumes a rare alpha/beta-barrel fold, consisting of 10 circularly arranged -strands surrounded by alpha-helices. Catalysis is performed in a hydrophobic reaction chamber at the center of the barrel
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Sepharose column chromatography, and gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli Rosetta(DE3) pLysS cells; expression in Escherichia coli
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expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E102Q
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mutation reduces the production of tryprostatin B to undetectable amounts
G115A
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no change in prenylation position of product
G115I
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complete loss of activity
G115L
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formation of tryprostatin B is abolished, formation of a new product occurs
G115T
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0.4% of wild-type activity in formation of trytrostatin B. Mutant catalyzes the formation of a different product that carries a reverse prenyl moiety at the C-3 of the indole nucleus
H279F
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70% of wild-type activity
Y205A
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mutant produces 70.3% C3-regularly prenylated product
Y205C
-
mutant produces 39.5% C3-regularly prenylated product
Y205D
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mutant produces 55.8% C3-regularly prenylated product and 3.6% C3-reversely prenylated product
Y205E
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mutant produces 57.6% C3-regularly prenylated product and 3% C3-reversely prenylated product
Y205F
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mutant produces 0.04% C3-regularly prenylated product
Y205G
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mutant produces 92% C3-regularly prenylated product and 12.2% C3-reversely prenylated product
Y205H
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mutant produces 60.7% C3-regularly prenylated product
Y205I
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mutant produces 39.5% C3-regularly prenylated product
Y205K
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mutant produces 110% C3-regularly prenylated product and 1.6% C3-reversely prenylated product
Y205L
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mutant produces 56.4% C3-regularly prenylated product
Y205M
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mutant produces 9.8% C3-regularly prenylated product
Y205N
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mutant produces 70% C3-regularly prenylated product and 2.8% C3-reversely prenylated product
Y205P
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mutant produces 38.7% C3-regularly prenylated product
Y205Q
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mutant produces 33.7% C3-regularly prenylated product
Y205R
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mutant produces 77% C3-regularly prenylated product and 13.2% C3-reversely prenylated product
Y205S
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mutant produces 50.4% C3-regularly prenylated product and 1.8% C3-reversely prenylated product
Y205T
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mutant does not produce C3-regularly prenylated product
Y205V
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mutant produces 33.0% C3-regularly prenylated product
Y205W
-
mutant does not produce C3-regularly prenylated product
E102Q
-
mutation reduces the production of tryprostatin B to undetectable amounts
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G115A
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no change in prenylation position of product
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G115L
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formation of tryprostatin B is abolished, formation of a new product occurs
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G115T
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0.4% of wild-type activity in formation of trytrostatin B. Mutant catalyzes the formation of a different product that carries a reverse prenyl moiety at the C-3 of the indole nucleus
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H279F
-
70% of wild-type activity
-
Y205A
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mutant produces 70.3% C3-regularly prenylated product
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Y205C
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mutant produces 39.5% C3-regularly prenylated product
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Y205F
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mutant produces 0.04% C3-regularly prenylated product
-
Y205L
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mutant produces 56.4% C3-regularly prenylated product
-
Y205M
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mutant produces 9.8% C3-regularly prenylated product
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine