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Information on EC 1.2.1.75 - malonyl-CoA reductase (malonate semialdehyde-forming)
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1.2.1.75 malonyl-CoA reductase (malonate semialdehyde-forming)IUBMB Comments
Requires Mg2+. Catalyses the reduction of malonyl-CoA to malonate semialdehyde, a key step in the 3-hydroxypropanoate and the 3-hydroxypropanoate/4-hydroxybutanoate cycles, autotrophic CO2 fixation pathways found in some green non-sulfur phototrophic bacteria and some thermoacidophilic archaea, respectively [1,2]. The enzyme from Sulfolobus tokodaii has been purified, and found to contain one RNA molecule per two subunits . The enzyme from Chloroflexus aurantiacus is bifunctional, and also catalyses the next reaction in the pathway, EC 1.1.1.298 [3-hydroxypropionate dehydrogenase (NADP+)] .
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The expected taxonomic range for this enzyme is: Bacteria, Archaea
Synonyms
malonate-semialdehyde dehydrogenase, malonyl CoA reductase (malonate semialdehyde-forming), malonyl-CoA reductase, MCR, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
malonyl CoA reductase (malonate semialdehyde-forming)
-
-
-
-
malonyl-CoA reductase
MCR
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
malonate semialdehyde + CoA + NADP+ = malonyl-CoA + NADPH + H+
-
-
-
-
malonate semialdehyde + CoA + NADP+ = malonyl-CoA + NADPH + H+
the protein acts as rigid template to press CoA and NADP into similar S-shaped, superimposable forms
malonate semialdehyde + CoA + NADP+ = malonyl-CoA + NADPH + H+
the protein acts as rigid template to press CoA and NADP into similar S-shaped, superimposable forms
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-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
malonate semialdehyde:NADP+ oxidoreductase (malonate semialdehyde-forming)
Requires Mg2+. Catalyses the reduction of malonyl-CoA to malonate semialdehyde, a key step in the 3-hydroxypropanoate and the 3-hydroxypropanoate/4-hydroxybutanoate cycles, autotrophic CO2 fixation pathways found in some green non-sulfur phototrophic bacteria and some thermoacidophilic archaea, respectively [1,2]. The enzyme from Sulfolobus tokodaii has been purified, and found to contain one RNA molecule per two subunits [3]. The enzyme from Chloroflexus aurantiacus is bifunctional, and also catalyses the next reaction in the pathway, EC 1.1.1.298 [3-hydroxypropionate dehydrogenase (NADP+)] [4].
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CAS REGISTRY NUMBER
COMMENTARY
429691-13-4
-
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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
malonate semialdehyde + coenzyme A + NADP+
malonyl-CoA + NADPH + H+
-
-
-
r
malonyl-CoA + NADPH + H+
malonate semialdehyde + NADP+ + CoA
-
-
-
-
?
succinate semialdehyde + coenzyme A + NADP+
succinyl-CoA + NADPH + H+
-
-
-
r
succinyl-CoA + NADPH + H+
succinate semialdehyde + coenzyme A + NADP+
at 25% of the rate with malonyl-CoA
-
-
r
additional information
?
-
-
enzyme additionally catalyzes the second reduction step of malonate semialdehyde + NADPH + H+ to 3-hydroxypropionate + NADP+. Reverse reaction starting with 3-hydroxypropionate does not require CoA and probably stops at malonate semialdehyde. No substrates are acetyl-CoA, propionyl-CoA, succinyl-CoA, or glyoxylate
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + CoA + NADP+
-
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + CoA + NADP+
-
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + CoA + NADP+
structural analysis reveals an unexpected reaction cycle in which NADP+ and CoA successively occupy identical binding sites, proposed reaction mechanism
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-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + CoA + NADP+
-
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + CoA + NADP+
structural analysis reveals an unexpected reaction cycle in which NADP+ and CoA successively occupy identical binding sites, proposed reaction mechanism
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + coenzyme A + NADP+
-
-
-
-
?
malonyl-CoA + NADPH + H+
malonate semialdehyde + coenzyme A + NADP+
-
-
-
r
succinyl-CoA + NADPH + H+
succinic semialdehyde + CoA + NADP+
-
-
-
?
succinyl-CoA + NADPH + H+
succinic semialdehyde + CoA + NADP+
-
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
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
7.8
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional aldehyde dehydrogenase plus alcohol dehydrogenase
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
the enzyme participates in the 3-hydroxypropionate/4-hydroxybutyrate cycle, an autotrophic CO2 fixation pathway found in some thermoacidophilic archaea
physiological function
the N-terminal region of MCR (MCR-N, amino acids 1-549) and the C-terminal region of MCR (MCR-C, amino acids 550-1219) are functionally distinct. Malonyl-CoA is reduced into free intermediate malonate semialdehyde with NADPH by the MCR-C fragment, and further reduced to 3-hydroxypropionate by the MCR-N fragment, the initial reduction of malonyl-CoA being rate limiting. The TGXXXG(A)X(1-2)G and YXXXK motifs are important for enzyme activities of both MCR-N and MCR-C fragments, and the enzyme activity increases when MCR is separated into two individual fragments. The MCR-C fragment has higher affinity for malonyl-CoA and 4-times higher Kcat/Km value than MCR
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MCR_METS5
Metallosphaera sedula (strain ATCC 51363 / DSM 5348 / JCM 9185 / NBRC 15509 / TH2)
357
0
39255
Swiss-Prot
-
MCR_SULTO
Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
359
0
39560
Swiss-Prot
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
39000
45000
39000
or dimer, 4 * 39000, calculated, 4 * 45000, SDS-PAGE, enzyme contains bound RNA
39000
or tetramer, 2 * 39000, calculated, 2 * 45000, SDS-PAGE, enzyme contains bound RNA
45000
or dimer, 4 * 39000, calculated, 4 * 45000, SDS-PAGE, enzyme contains bound RNA
45000
or tetramer, 2 * 39000, calculated, 2 * 45000, SDS-PAGE, enzyme contains bound RNA
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homotetramer
tetramer
additional information
enzyme in its native state is associated with small RNA
dimer
or tetramer, 2 * 39000, calculated, 2 * 45000, SDS-PAGE, enzyme contains bound RNA
tetramer
or dimer, 4 * 39000, calculated, 4 * 45000, SDS-PAGE, enzyme contains bound RNA
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
malonyl-CoA reductase in the substrate-free state at 2.05 A resolution and in complex with NADP+ at 1.9 A resolution and in complex with CoA at 2.4 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
additional information
synthesis
heterologous expression of the malonyl-CoA dependent pathway genes malonyl-CoA reductase and malonate semialdehyde reductase enables Synechococcus elongatus to synthesize 3-hydroxypropionic acid to a final titer of 665 mg/l
synthesis
-
heterologous expression of the malonyl-CoA dependent pathway genes malonyl-CoA reductase and malonate semialdehyde reductase enables Synechococcus elongatus to synthesize 3-hydroxypropionic acid to a final titer of 665 mg/l
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additional information
the crystallographic data indicate how to construct a bispecific cofactor binding site and to engineer a malonyl-CoA into methylmalonyl-CoA reductase for polyester building block production
additional information
-
the crystallographic data indicate how to construct a bispecific cofactor binding site and to engineer a malonyl-CoA into methylmalonyl-CoA reductase for polyester building block production
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme purified by heat precipitation at 85°C and concentration by ultrafiltration, gel filtration chromatography using a Superdex 200 HR 26/60 gel filtration column and Resource phenyl chromatography using a Resource phenyl column
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Escherichia coli Rosetta 2 cells transformed with pTrc99A-Mcr plasmid harbouring mcr gene from Sulfolobus tokodaii
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
extracts of autotrophically grown cells exhibit an NADPH-dependent succinyl-CoA reductase activity of 200 nM/min*mg of soluble protein, whereas extracts of heterotrophically grown cells exhibit an activity of 10 nM/min*mg of protein
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in heterotropically grown cells, activity is downregulated to 40 nmol per min and mg
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
synthesis
biotechnology
the crystallographic data indicate how to construct a bispecific cofactor binding site and to engineer a malonyl-CoA into methylmalonyl-CoA reductase for polyester building block production
biotechnology
-
the crystallographic data indicate how to construct a bispecific cofactor binding site and to engineer a malonyl-CoA into methylmalonyl-CoA reductase for polyester building block production
-
synthesis
MCR is of biotechnological interest for the synthesis of polyester building blocks
synthesis
integration of multiple copies of malonyl-CoA reductase MCR and of phosphorylation-deficient acetyl-CoA carboxylase ACC1 genes into the genome of yeast increases 3-hydroxypropionic acid titer fivefold in comparison with single integration. Optimizing the supply of acetyl-CoA by overexpressing native pyruvate decarboxylase PDC1, aldehyde dehydrogenase ALD6, and acetyl-CoA synthase from Salmonella enterica SEacsL641P engineering the cofactor specificity of the glyceraldehyde-3-phosphate dehydrogenase to increase the intracellular production of NADPH at the expense of NADH improves 3-hydroxypropionic acid production and reduces formation of glycerol as by-product. The final strain produces 9.8 g per L 3-hydroxypropionic acid with a yield of 13% C-mol per C-mol glucose after 100 h in carbon-limited fed-batch cultivation at pH 5
synthesis
the combination of Escherichia coli BL21(DE3) and pET28a carrying heterogeneous acetyl-CoA carboxylase (Acc) from Corynebacterium glutamicum and codon-optimized malonyl-CoA reductase (MCR) from Chloroflexus aurantiacus is the most efficient host-vector system for 3-hydroxypropionic acid production, and the highest concentration of 3-hydroxypropionic attained in shake flask cultivation reaches 1.80 g/l with induction at 0.25 mM IPTG and 25°C, and supplementation of NaHCO3 and biotin
synthesis
-
MCR is of biotechnological interest for the synthesis of polyester building blocks
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Strauss, G.; Fuchs, G.
Enzymes of a novel autotrophic carbon dioxide fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle
Eur. J. Biochem.
215
633-643
1993
Chloroflexus aurantiacus
brenda
Huegler, M.; Menendez, C.; Schaegger, H.; Fuchs, G.
Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO(2) fixation
J. Bacteriol.
184
2404-2410
2002
Chloroflexus aurantiacus
brenda
Alber, B.; Olinger, M.; Rieder, A.; Kockelkorn, D.; Jobst, B.; Hägler, M.; Fuchs, G.
Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp
J. Bacteriol.
188
8551-8559
2006
Metallosphaera sedula, Sulfurisphaera tokodaii (Q96YK1)
brenda
Demmer, U.; Warkentin, E.; Srivastava, A.; Kockelkorn, D.; Pötter, M.; Marx, A.; Fuchs, G.; Ermler, U.
Structural basis for a bispecific NADP+ and CoA binding site in an archaeal malonyl-coenzyme A reductase
J. Biol. Chem.
288
6363-6370
2013
Sulfurisphaera tokodaii (Q96YK1), Sulfurisphaera tokodaii DSM 16993 (Q96YK1)
brenda
Cheng, Z.; Jiang, J.; Wu, H.; Li, Z.; Ye, Q.
Enhanced production of 3-hydroxypropionic acid from glucose via malonyl-CoA pathway by engineered Escherichia coli
Biores. Technol.
200
897-904
2016
Chloroflexus aurantiacus (Q6QQP7)
brenda
Lan, E.I.; Chuang, D.S.; Shen, C.R.; Lee, A.M.; Ro, S.Y.; Liao, J.C.
Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using Synechococcus elongatus PCC 7942
Metab. Eng.
31
163-170
2015
Sulfurisphaera tokodaii (Q96YK1), Sulfurisphaera tokodaii DSM 16993 (Q96YK1)
brenda
Kildegaard, K.; Jensen, N.; Schneider, K.; Czarnotta, E.; Özdemir, E.; Klein, T.; Maury, J.; Ebert, B.; Christensen, H.; Chen, Y.; Kim, I.; Herrgard, M.; Blank, L.; Forster, J.; Nielsen, J.; Borodina, I.
Engineering and systems-level analysis of Saccharomyces cerevisiae for production of 3-hydroxypropionic acid via malonyl-CoA reductase-dependent pathway
Microb. Cell Fact.
15
53
2016
Chloroflexus aurantiacus (Q6QQP7)
brenda
Liu, C.; Wang, Q.; Xian, M.; Ding, Y.; Zhao, G.
Dissection of malonyl-coenzyme A reductase of Chloroflexus aurantiacus results in enzyme activity improvement
PLoS ONE
8
e75554
2013
Chloroflexus aurantiacus (Q6QQP7)
brenda
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