BRENDA - Enzyme Database
show all sequences of 4.2.3.9

Aristolochene synthase: mechanistic analysis of active site residues by site-directed mutagenesis

Felicetti, B.; Cane, D.E.; J. Am. Chem. Soc. 126, 7212-7221 (2004)

Data extracted from this reference:

Engineering
Amino acid exchange
Commentary
Organism
D115E
kcat/KM is 12fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 75:6:119
Penicillium roqueforti
D115N
inactive mutant enzyme
Penicillium roqueforti
D116E
kcat/KM is 60fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 62:3:35
Penicillium roqueforti
D116N
kcat/KM is 48fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 63:2:35
Penicillium roqueforti
E119D
kcat/KM is 2.4fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 94:2:4
Penicillium roqueforti
E119Q
kcat/KM is 2.3fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 84:2:14
Penicillium roqueforti
E227D
kcat/KM is 1182fold higher than wild-type value, in contrast to wild-type enzyme that exclusively produces aristolochene from trans,trans-farnesyl diphosphate, the mutant enzyme produces 26% aristolochene and 74% germacrene A
Aspergillus terreus
E227Q
inactive mutant enzyme
Aspergillus terreus
E252D
kcat/KM is 111fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 19:0:81
Penicillium roqueforti
E252Q
mutant enzyme produces only (-)-germacrene A
Penicillium roqueforti
N219D
kcat/KM is 6667fold higher than wild-type value, in contrast to wild-type enzyme that exclusively produces aristolochene from trans,trans-farnesyl diphosphate, the mutant enzyme produces 44% aristolochene and 56% germacrene A
Aspergillus terreus
N244D
kcat/KM is 1978fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 19:0:81
Penicillium roqueforti
N244L
inactive mutant enzyme
Penicillium roqueforti
S248A
kcat/KM is 300fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 21:0:79
Penicillium roqueforti
S248A/E252D
inactive mutant enzyme
Penicillium roqueforti
Y92F
100fold reduction in kcat, 50fold decrease in KM, resulting in 2fold decrease in kcat/Km. The mutant enzyme produces (+)-aristolochene as 81% of the product, 7% (-)-valencene and 12% (S)-(-)-germacrene A
Penicillium roqueforti
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.000012
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme Y92F
Penicillium roqueforti
0.00015
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119Q
Penicillium roqueforti
0.00032
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119D
Penicillium roqueforti
0.0006
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Penicillium roqueforti
0.0011
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116E
Penicillium roqueforti
0.0013
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Aspergillus terreus
0.0014
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E227D
Aspergillus terreus
0.0015
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116N
Penicillium roqueforti
0.0027
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D115E
Penicillium roqueforti
0.0033
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N244D
Penicillium roqueforti
0.0034
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252D
Penicillium roqueforti
0.0039
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N219D
Aspergillus terreus
0.0055
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme S248A
Penicillium roqueforti
0.0101
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252Q
Penicillium roqueforti
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Aspergillus terreus
-
-
-
Penicillium roqueforti
Q03471
-
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
trans,trans-farnesyl diphosphate
-
665301
Penicillium roqueforti
(+)-aristolochene + diphosphate
(+)-aristolochene + minor amounts of (S)-(-)-germacrene A and (-)-valencene in a 94:4:2 ratio
-
-
?
trans,trans-farnesyl diphosphate
-
665301
Aspergillus terreus
(+)-aristolochene + diphosphate
(+)-aristolochene is the only product
-
-
?
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.000076
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N219D
Aspergillus terreus
0.00012
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N244D
Penicillium roqueforti
0.00022
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252Q
Penicillium roqueforti
0.0004
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme Y92F
Penicillium roqueforti
0.0013
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116E; pH 8.0, 30°C, mutant enzyme S248A
Penicillium roqueforti
0.0016
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E227D
Aspergillus terreus
0.0022
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116N; pH 8.0, 30°C, mutant enzyme E252D
Penicillium roqueforti
0.0048
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119Q
Penicillium roqueforti
0.0097
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119D
Penicillium roqueforti
0.0162
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D115E
Penicillium roqueforti
0.0173
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Aspergillus terreus
0.043
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Penicillium roqueforti
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
D115E
kcat/KM is 12fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 75:6:119
Penicillium roqueforti
D115N
inactive mutant enzyme
Penicillium roqueforti
D116E
kcat/KM is 60fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 62:3:35
Penicillium roqueforti
D116N
kcat/KM is 48fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 63:2:35
Penicillium roqueforti
E119D
kcat/KM is 2.4fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 94:2:4
Penicillium roqueforti
E119Q
kcat/KM is 2.3fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 84:2:14
Penicillium roqueforti
E227D
kcat/KM is 1182fold higher than wild-type value, in contrast to wild-type enzyme that exclusively produces aristolochene from trans,trans-farnesyl diphosphate, the mutant enzyme produces 26% aristolochene and 74% germacrene A
Aspergillus terreus
E227Q
inactive mutant enzyme
Aspergillus terreus
E252D
kcat/KM is 111fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 19:0:81
Penicillium roqueforti
E252Q
mutant enzyme produces only (-)-germacrene A
Penicillium roqueforti
N219D
kcat/KM is 6667fold higher than wild-type value, in contrast to wild-type enzyme that exclusively produces aristolochene from trans,trans-farnesyl diphosphate, the mutant enzyme produces 44% aristolochene and 56% germacrene A
Aspergillus terreus
N244D
kcat/KM is 1978fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 19:0:81
Penicillium roqueforti
N244L
inactive mutant enzyme
Penicillium roqueforti
S248A
kcat/KM is 300fold lower than wild-type value. Wild-type enzyme produces (+)-aristolochene, (-)-valencene and (S)-(-)-germacrene A in the ratio 93:2:4, the ratio of the mutant enzyme is 21:0:79
Penicillium roqueforti
S248A/E252D
inactive mutant enzyme
Penicillium roqueforti
Y92F
100fold reduction in kcat, 50fold decrease in KM, resulting in 2fold decrease in kcat/Km. The mutant enzyme produces (+)-aristolochene as 81% of the product, 7% (-)-valencene and 12% (S)-(-)-germacrene A
Penicillium roqueforti
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.000012
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme Y92F
Penicillium roqueforti
0.00015
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119Q
Penicillium roqueforti
0.00032
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119D
Penicillium roqueforti
0.0006
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Penicillium roqueforti
0.0011
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116E
Penicillium roqueforti
0.0013
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Aspergillus terreus
0.0014
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E227D
Aspergillus terreus
0.0015
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116N
Penicillium roqueforti
0.0027
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D115E
Penicillium roqueforti
0.0033
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N244D
Penicillium roqueforti
0.0034
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252D
Penicillium roqueforti
0.0039
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N219D
Aspergillus terreus
0.0055
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme S248A
Penicillium roqueforti
0.0101
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252Q
Penicillium roqueforti
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
trans,trans-farnesyl diphosphate
-
665301
Penicillium roqueforti
(+)-aristolochene + diphosphate
(+)-aristolochene + minor amounts of (S)-(-)-germacrene A and (-)-valencene in a 94:4:2 ratio
-
-
?
trans,trans-farnesyl diphosphate
-
665301
Aspergillus terreus
(+)-aristolochene + diphosphate
(+)-aristolochene is the only product
-
-
?
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.000076
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N219D
Aspergillus terreus
0.00012
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme N244D
Penicillium roqueforti
0.00022
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E252Q
Penicillium roqueforti
0.0004
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme Y92F
Penicillium roqueforti
0.0013
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116E; pH 8.0, 30°C, mutant enzyme S248A
Penicillium roqueforti
0.0016
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E227D
Aspergillus terreus
0.0022
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D116N; pH 8.0, 30°C, mutant enzyme E252D
Penicillium roqueforti
0.0048
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119Q
Penicillium roqueforti
0.0097
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme E119D
Penicillium roqueforti
0.0162
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, mutant enzyme D115E
Penicillium roqueforti
0.0173
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Aspergillus terreus
0.043
-
trans,trans-farnesyl diphosphate
pH 8.0, 30°C, wild-type enzyme
Penicillium roqueforti
Other publictions for EC 4.2.3.9
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
747103
Chen
Probing the role of active si ...
Aspergillus terreus
Biochemistry
55
2864-2874
2016
-
-
-
1
9
-
-
7
-
1
-
1
-
1
-
-
1
-
-
-
-
-
2
-
-
-
-
8
-
-
-
-
-
-
-
-
-
-
-
1
9
-
-
-
-
7
-
1
-
1
-
-
-
1
-
-
-
-
2
-
-
-
-
8
-
-
-
-
-
-
-
-
7
7
747509
Faraldos
Enzymatic synthesis of natura ...
Penicillium roqueforti
Chem. Commun. (Camb.)
52
14027-14030
2016
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
746589
Rising
Formation of a novel macrocyc ...
Nicotiana tabacum
ACS Chem. Biol.
10
1729-1736
2015
-
-
1
1
-
-
1
2
-
-
-
1
-
2
-
-
1
-
-
-
-
-
2
-
-
-
-
2
-
-
-
-
1
-
-
-
-
1
-
1
-
-
-
1
1
2
-
-
-
1
-
-
-
1
-
-
-
-
2
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
729236
Chen
Mechanistic insights from the ...
Aspergillus terreus
Biochemistry
52
5441-5453
2013
-
-
1
1
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
729242
van der Kamp
Conformational change and liga ...
Aspergillus terreus
Biochemistry
52
8094-8105
2013
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
729580
Faraldos
The role of aristolochene synt ...
Penicillium roqueforti
Chem. Commun. (Camb. )
48
3230-3232
2012
-
-
-
-
9
-
-
7
-
-
-
-
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
7
-
-
-
-
-
-
-
-
-
-
-
-
9
-
-
-
-
7
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
7
-
-
-
-
-
-
-
-
7
7
715288
Faraldos
Probing eudesmane cation-pi in ...
Penicillium roqueforti
J. Am. Chem. Soc.
133
13906-13909
2011
-
-
1
-
5
-
-
5
-
-
-
-
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
5
-
-
-
-
-
-
-
-
-
1
-
-
5
-
-
-
-
5
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
5
-
-
-
-
-
-
-
-
5
5
716415
Faraldos
Templating effects in aristolo ...
Penicillium roqueforti
Org. Biomol. Chem.
9
6920-6923
2011
-
-
-
-
8
-
-
9
-
-
-
-
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
9
-
-
-
-
-
-
-
-
-
-
-
-
8
-
-
-
-
9
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
9
-
-
-
-
-
-
-
-
9
9
716419
Faraldos
Inhibition of (+)-aristolochen ...
Penicillium roqueforti
Org. Lett.
13
1202-1205
2011
-
-
-
-
-
-
2
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
704204
Faraldos
Bisabolyl-derived sesquiterpen ...
Nicotiana tabacum
J. Am. Chem. Soc.
132
4281-4289
2010
-
-
-
-
-
-
-
1
-
1
-
-
-
2
-
-
-
-
-
-
-
-
2
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
1
-
-
-
-
-
-
-
-
2
2
705304
Faraldos
Intermediacy of eudesmane cati ...
Penicillium roqueforti
J. Org. Chem.
75
1119-1125
2010
-
-
1
-
-
-
2
1
-
1
1
-
-
2
-
-
1
-
-
-
-
-
1
1
-
-
-
1
-
-
-
-
2
-
-
-
-
1
-
-
-
-
-
2
2
1
-
1
1
-
-
-
-
1
-
-
-
-
1
1
-
-
-
1
-
-
-
-
-
-
-
-
1
1
706047
Miller
6- and 14-Fluoro farnesyl diph ...
Penicillium roqueforti
Org. Biomol. Chem.
7
962-975
2009
-
-
1
-
-
-
-
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
691962
Christianson
Unearthing the roots of the te ...
Aspergillus terreus
Curr. Opin. Chem. Biol.
12
141-150
2008
-
-
-
-
-
-
-
-
-
1
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
693062
Shishova
X-ray crystallographic studies ...
Aspergillus terreus
J. Biol. Chem.
283
15431-15439
2008
-
-
1
1
-
-
1
-
-
1
-
1
-
2
-
-
1
-
-
-
-
-
2
2
1
-
-
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
1
-
1
-
-
-
1
-
-
-
-
2
2
1
-
-
-
1
-
-
-
-
-
-
-
-
-
694515
Miller
Stereochemistry of eudesmane c ...
Penicillium roqueforti
Org. Biomol. Chem.
6
2346-2354
2008
-
-
1
-
1
-
-
1
-
1
-
2
-
2
-
-
1
-
-
-
-
-
2
-
1
-
-
1
1
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
1
-
1
-
2
-
-
-
1
-
-
-
-
2
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
678256
Shishova
X-ray crystal structure of ari ...
Aspergillus terreus
Biochemistry
46
1941-1951
2007
-
-
1
1
-
-
-
-
-
1
1
1
-
3
-
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
1
1
1
-
-
-
1
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
679187
Yu
Probing the reaction mechanism ...
Escherichia coli
Chem. Commun. (Camb. )
2007
4155-4157
2007
-
-
1
-
-
-
2
1
-
-
-
1
-
1
-
-
1
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
2
-
-
-
-
1
-
-
-
-
-
2
2
1
-
-
-
1
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
679218
Miller
Aristolochene synthase-catalyz ...
Penicillium roqueforti
ChemBioChem
8
1819-1825
2007
-
-
1
-
-
-
-
-
-
1
-
1
-
2
-
-
1
-
1
-
-
-
2
-
1
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
1
-
-
-
2
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
680359
Allemann
Synthetic efficiency in enzyme ...
Penicillium roqueforti
J. Am. Chem. Soc.
129
13008-13013
2007
-
-
-
-
-
-
-
-
-
1
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
682226
Miller
Competitive inhibition of aris ...
Penicillium roqueforti
Org. Biomol. Chem.
5
3287-3298
2007
-
-
-
-
-
-
3
-
-
1
-
1
-
2
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
3
-
-
-
-
-
-
-
-
-
-
3
3
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
682223
Forcat
Stabilisation of transition st ...
Penicillium roqueforti
Org. Biomol. Chem.
4
2563-2567
2006
-
-
1
-
7
-
-
8
-
1
-
1
-
2
-
-
1
-
1
-
-
-
2
1
1
-
-
16
1
-
-
-
-
-
-
-
-
1
-
-
7
-
-
-
-
8
-
1
-
1
-
-
-
1
1
-
-
-
2
1
1
-
-
16
1
-
-
-
-
-
-
-
-
-
664584
Forcat
Dual role for phenylalanine 17 ...
Penicillium roqueforti
Chem. Commun. (Camb.)
2004
2094-2095
2004
-
-
-
-
2
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
665301
Felicetti
Aristolochene synthase: mechan ...
Aspergillus terreus, Penicillium roqueforti
J. Am. Chem. Soc.
126
7212-7221
2004
-
-
-
-
16
-
-
14
-
-
-
-
-
4
-
-
-
-
-
-
-
-
2
-
-
-
-
12
-
-
-
-
-
-
-
-
-
-
-
-
16
-
-
-
-
14
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
12
-
-
-
-
-
-
-
-
-
-
644243
Deligeorgopoulou
Evidence for differential fold ...
Penicillium roqueforti
Biochemistry
42
7741-7747
2003
-
-
1
-
4
-
-
5
-
-
-
-
-
3
-
-
1
-
-
-
-
-
2
-
-
-
-
5
-
-
-
-
-
-
-
-
-
1
-
-
6
-
-
-
-
5
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
5
-
-
-
-
-
-
-
-
3
3
644241
Calvert
-
Tyrosine 92 of aristolochene s ...
Penicillium roqueforti
Chem. Commun. (Camb.)
2002
2384-2385
2002
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644242
Calvert
Germacrene A is a product of t ...
Penicillium roqueforti
J. Am. Chem. Soc.
124
11636-11641
2002
-
-
1
-
1
-
-
2
-
-
-
-
-
2
-
-
1
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
644240
Caruthers
Crystal structure determinatio ...
Penicillium roqueforti
J. Biol. Chem.
275
25533-25539
2000
-
-
-
1
-
-
-
-
-
-
-
-
-
3
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644244
Cane
Aristolochene synthase: purifi ...
Aspergillus terreus, Penicillium roqueforti
Arch. Biochem. Biophys.
376
354-364
2000
-
-
1
-
-
-
3
3
-
5
2
-
-
6
-
-
1
-
-
-
1
-
2
2
-
-
-
3
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
3
-
3
-
5
2
-
-
-
-
1
-
-
1
-
2
2
-
-
-
3
1
-
-
-
-
-
-
-
-
-
644239
Proctor
Aristolochene synthase. Isolat ...
Penicillium roqueforti
J. Biol. Chem.
268
4543-4548
1993
-
-
1
-
-
-
-
-
-
-
1
1
-
5
-
-
-
-
-
1
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
-
-
1
-
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644236
Cane
-
Aristolochene biosynthesis. St ...
Aspergillus terreus
J. Am. Chem. Soc.
112
3209-3210
1990
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644237
Cane
-
Aristolochene biosynthesis and ...
Aspergillus terreus
J. Am. Chem. Soc.
111
8914-8916
1989
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
644238
Hohn
Purification and characterizat ...
Penicillium roqueforti
Arch. Biochem. Biophys.
272
137-143
1989
-
-
-
-
-
-
2
1
-
2
2
-
-
2
-
-
1
-
-
-
1
-
1
1
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
1
-
2
2
-
-
-
-
1
-
-
1
-
1
1
-
-
-
-
1
-
-
-
-
-
-
-
-
-