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Information on EC 4.1.1.6 - cis-aconitate decarboxylase
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4.1.1.6 cis-aconitate decarboxylaseIUBMB Comments
The enzyme has been characterized from the fungus Aspergillus terreus and from human macrophages. cf. EC 4.1.1.113, trans-aconitate decarboxylase.
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Word Map
- 4.1.1.6
-
itaconic
- terreus
- aspergillus
- niger
- aconitase
- citrate
-
citric
- glutamicum
- isocitrate
-
titre
-
oxalic
- 6-phosphofructo-1-kinase
-
high-value
-
luria-bertani
-
dicarboxylic
- industry
The enzyme appears in viruses and cellular organisms
Synonyms
Aconitate decarboxylase, CAD, CAD1, CadA, cis-aconitate decarboxylase, cis-Aconitic acid decarboxylase, Decarboxylase, aconitate, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Aconitate decarboxylase
-
-
-
-
CAD
CAD1
CadA
cis-aconitate decarboxylase
cis-Aconitic acid decarboxylase
Decarboxylase, aconitate
-
-
-
-
cis-aconitate decarboxylase
-
-
cis-Aconitic acid decarboxylase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cis-aconitate = itaconate + CO2
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
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-
-
-
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SYSTEMATIC NAME
IUBMB Comments
cis-aconitate carboxy-lyase (itaconate-forming)
The enzyme has been characterized from the fungus Aspergillus terreus and from human macrophages. cf. EC 4.1.1.113, trans-aconitate decarboxylase.
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CAS REGISTRY NUMBER
COMMENTARY
9025-01-8
-
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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
cis-aconitate
?
-
enzyme is involved in biosynthesis of itaconate
-
-
-
cis-aconitate
itaconate + CO2
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-
-
-
?
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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
cis-aconitate
?
-
enzyme is involved in biosynthesis of itaconate
-
-
-
cis-aconitate
itaconate + CO2
-
-
-
-
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Fluorocitrate
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inhibits citrate decarboxylation, no inhibition of decarboxylation of cis-aconitate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Tween 80
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Tween 80 at a concentration of 0.1% resulted in a slight (7%) increase in conversion activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.2
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 8
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about 20% activity at pH 5.0, 100% activity at pH 5.5, about 65% activity at pH 6.0, about 50% activity at pH 6.5, about 35% activity at pH 7.0, about 25% activity at pH 7.5, about 20% activity at pH 8.0
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 40
-
more than 60% activity at 25 and 40°C, about 90% activity at 30°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
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under conditions of itaconate production. Absent from growing mycelia
brenda
additional information
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production of itaconic acid is achieved by the fermentation with Aspergillus terreus on sugar-containing media
brenda
additional information
-
production of itaconic acid is achieved by the fermentation with Aspergillus terreus on sugar-containing media
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
metabolism
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in the first steps of the citric acid cycle, citrate and cis-aconitate are formed, the enzymes preceding in the pathway, namely citrate synthase and aconitase, are found in the mitochondria. In the last step, the only itaconic acid pathway dedicated step, cis-aconitate decarboxylase (CadA) forms itaconic acid releasing carbon dioxide in the cytosol
metabolism
-
in the first steps of the citric acid cycle, citrate and cis-aconitate are formed, the enzymes preceding in the pathway, namely citrate synthase and aconitase, are found in the mitochondria. In the last step, the only itaconic acid pathway dedicated step, cis-aconitate decarboxylase (CadA) forms itaconic acid releasing carbon dioxide in the cytosol
metabolism
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in the first steps of the citric acid cycle, citrate and cis-aconitate are formed, the enzymes preceding in the pathway, namely citrate synthase and aconitase, are found in the mitochondria. In the last step, the only itaconic acid pathway dedicated step, cis-aconitate decarboxylase (CadA) forms itaconic acid releasing carbon dioxide in the cytosol
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CAD_ASPTN
Aspergillus terreus (strain NIH 2624 / FGSC A1156)
490
0
52950
Swiss-Prot
A0A1M9GEQ6_9MYCO
459
0
48193
TrEMBL
A0A1M8YQ03_9MYCO
458
0
48376
TrEMBL
A0A1M8XCJ7_9MYCO
461
0
48440
TrEMBL
A0A1M8MGX3_9MYCO
473
0
50605
TrEMBL
A0A1M9AI60_9MYCO
478
0
49922
TrEMBL
A0A1M8S831_9MYCO
457
0
49228
TrEMBL
A0A1M8WQ82_9MYCO
450
0
48132
TrEMBL
A0A1M9H5V0_9MYCO
450
0
47798
TrEMBL
I7GGR1_MYCS2
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
477
0
50880
TrEMBL
A0A1M9ARK7_9MYCO
462
0
47468
TrEMBL
A0A1U3SFP4_9MYCO
448
0
47855
TrEMBL
A0A1M8XCZ0_9MYCO
458
0
47998
TrEMBL
A0A1M8SHK4_9MYCO
464
0
48471
TrEMBL
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
mutant strain which produces higher concentrations of itaconic acid is provoked by N-methyl N'-nitro-N-nitrosoguanidine treatment
additional information
-
a truncated version of the Aspergillus niger pfkA gene exhibits a higher citric acid yield due to a reduced inhibition by citrate and ATP, the truncated pfkA version has also a positive impact on the itaconic acid accumulation when expressed in Aspergillus terreus
additional information
-
a truncated version of the Aspergillus niger pfkA gene exhibits a higher citric acid yield due to a reduced inhibition by citrate and ATP, the truncated pfkA version has also a positive impact on the itaconic acid accumulation when expressed in Aspergillus terreus
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no loss of activity after dialysis for 2 h at 0°C against 0.05 M phosphate buffer, pH 7. Inactivation after 15 h
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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 and in Aspergillus niger strain AB 1.13
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gene cadA, heterologous expression in Aspergillus niger strain N201, expression of two previously identified Aspergillus terreus genes encoding putative organic acid transporters, genes mttA and mfsA, increases itaconic acid production in an Aspergillus niger cis-aconitate decarboxylase expressing strain, production method optimization, overview
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gene cadA, heterologous functional expression in citric acid producing Aspergillus niger under various constitutive promoters of different expression strength, heterologous expression of the gene in Saccharomyces cerevisiae
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gene cadA, the cadA gene of is located in a gene cluster together with two transporters, one a putative mitochondrial carrier, the other a putative plasma membrane carrier, cloning in Escherichia coli strain TOP10, heterologous mitochondrial and cytosolic expression of the enzyme in Aspergillus niger strain ATCC 1015, the mitochondrial expression doubles the enzyme productivity compared to the cytosolic expression. Co-expression of a cytosolic or a mitochondrial aconitase with cytosolic CadA leads to a significant increase of itaconic acid production compared to cytsolic CadA expression alone. The rate-limiting step for itaconic acid production under these conditions appears to be both the provision of cis-aconitate as a substrate for the CadA as well as the CAD activity itself
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
industry
economic production of itaconic acid which is a supplement in many products
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bentley, R.; Thiessen, C.P.
Biosynthesis of itaconic acid in Aspergillus terreus
J. Biol. Chem.
226
703-720
1957
Aspergillus terreus
brenda
Bonnarme, P.; Gillet, B.; Sepulchre, A.M.; Role, C.; Beloeil, J.C.; Ducrocq, C.
Itaconate biosynthesis in Aspergillus terreus
J. Bacteriol.
177
3573-3578
1995
Aspergillus terreus
brenda
Jaklitsch, W.M.; Kubicek, C.P.; Scrutton, M.C.
The subcellular organization of itaconate biosynthesis in Aspergillus terreus
J. Gen. Microbiol.
137
533-539
1991
Aspergillus terreus
-
brenda
Kanamasa, S.; Dwiarti, L.; Okabe, M.; Park, E.Y.
Cloning and functional characterization of the cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus
Appl. Microbiol. Biotechnol.
80
223-229
2008
Aspergillus terreus, Aspergillus terreus (B3IUN8)
brenda
Okabe, M.; Lies, D.; Kanamasa, S.; Park, E.Y.
Biotechnological production of itaconic acid and its biosynthesis in Aspergillus terreus
Appl. Microbiol. Biotechnol.
84
597-606
2009
Aspergillus terreus, Aspergillus terreus (B3IUN8)
brenda
Li, M.; Zhang, H.; Hong, L.; Jin, Y.; Gong, T.; Sun, L.; Yang, J.; Zheng, X.
Preparation and characterization of a novel monoclonal antibody specific to human CAD protein
Hybridoma
28
129-132
2009
Aspergillus terreus, Homo sapiens
brenda
Tevz, G.; Bencina, M.; Legisa, M.
Enhancing itaconic acid production by Aspergillus terreus
Appl. Microbiol. Biotechnol.
87
1657-1664
2010
Aspergillus terreus
brenda
Li, A.; van Luijk, N.; ter Beek, M.; Caspers, M.; Punt, P.; van der Werf, M.
A clone-based transcriptomics approach for the identification of genes relevant for itaconic acid production in Aspergillus
Fungal Genet. Biol.
48
602-611
2011
Aspergillus terreus, Aspergillus terreus NRRL1960
brenda
Michelucci, A.; Cordes, T.; Ghelfi, J.; Pailot, A.; Reiling, N.; Goldmann, O.; Binz, T.; Wegner, A.; Tallam, A.; Rausell, A.; Buttini, M.; Linster, C.L.; Medina, E.; Balling, R.; Hiller, K.
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Proc. Natl. Acad. Sci. USA
110
7820-7825
2013
Homo sapiens (A6NK06), Mus musculus (P54987)
brenda
Li, A.; Pfelzer, N.; Zuijderwijk, R.; Brickwedde, A.; van Zeijl, C.; Punt, P.
Reduced by-product formation and modified oxygen availability improve itaconic acid production in Aspergillus niger
Appl. Microbiol. Biotechnol.
97
3901-3911
2013
Aspergillus terreus
brenda
Steiger, M.G.; Blumhoff, M.L.; Mattanovich, D.; Sauer, M.
Biochemistry of microbial itaconic acid production
Front. Microbiol.
4
23
2013
Aspergillus itaconicus, Aspergillus terreus, Aspergillus terreus NRRL1960
brenda
Sugimoto, T.; Kato, T.; Park, E.Y.
Functional analysis of cis-aconitate decarboxylase and trans-aconitate metabolism in riboflavin-producing filamentous Ashbya gossypii
J. Biosci. Bioeng.
117
563-568
2014
no activity in Ashbya gossypii
brenda
Blumhoff, M.L.; Steiger, M.G.; Mattanovich, D.; Sauer, M.
Targeting enzymes to the right compartment: metabolic engineering for itaconic acid production by Aspergillus niger
Metab. Eng.
19
26-32
2013
Aspergillus terreus
brenda
Vuoristo, K.S.; Mars, A.E.; Sangra, J.V.; Springer, J.; Eggink, G.; Sanders, J.P.; Weusthuis, R.A.
Metabolic engineering of itaconate production in Escherichia coli
Appl. Microbiol. Biotechnol.
99
221-228
2015
Aspergillus terreus
brenda
Yamamoto, K.; Nagata, K.; Ohara, H.; Aso, Y.
Challenges in the production of itaconic acid by metabolically engineered Escherichia coli
Bioengineered
6
303-306
2015
Aspergillus terreus
brenda
Noh, M.H.; Lim, H.G.; Woo, S.H.; Song, J.; Jung, G.Y.
Production of itaconic acid from acetate by engineering acid-tolerant Escherichia coli W
Biotechnol. Bioeng.
115
729-738
2018
Aspergillus terreus
brenda
Bafana, R.; Sivanesan, S.; Pandey, R.A.
Itaconic acid production by filamentous fungi in starch-rich industrial residues
Indian J. Microbiol.
57
322-328
2017
Aspergillus terreus (A0A223A3W7), Aspergillus terreus, Aspergillus terreus C1 (A0A223A3W7), Aspergillus terreus C2 (A0A223A3W7)
brenda
Otten, A.; Brocker, M.; Bott, M.
Metabolic engineering of Corynebacterium glutamicum for the production of itaconate
Metab. Eng.
30
156-165
2015
Aspergillus terreus
brenda
Huang, X.; Lu, X.; Li, Y.; Li, X.; Li, J.J.
Improving itaconic acid production through genetic engineering of an industrial Aspergillus terreus strain
Microb. Cell Fact.
13
119
2014
Aspergillus terreus, Aspergillus terreus LYT10
brenda
Kim, J.; Seo, H.M.; Bhatia, S.K.; Song, H.S.; Kim, J.H.; Jeon, J.M.; Choi, K.Y.; Kim, W.; Yoon, J.J.; Kim, Y.G.; Yang, Y.H.
Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli
Sci. Rep.
7
39768
2017
Aspergillus terreus
brenda
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