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Literature summary for 1.1.1.247 extracted from

  • Dastmalchi, M.; Chang, L.; Torres, M.; Ng, K.; Facchini, P.
    Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy (2018), Plant J., 95, 631-647 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
isozyme COR-B, DNA and amino acid sequence determination and analysis, sequence comparison with codeinone reductase isoforms COR1.2, COR1.3, COR1.4, and COR1.1, quantitative real-time PCR expression analysis, recombinant coexpression of isozyme COR-B with thebaine 6-O-demethylase (T6ODM) in Saccharomyces cerevisiae strain CEN.PK fed with thebaine Papaver somniferum
isozyme COR1.1, DNA and amino acid sequence determination and analysis, sequence comparison with codeinone reductase isoforms COR1.2, COR1.3, COR1.4, and COR-B, quantitative real-time PCR expression analysis Papaver somniferum
isozyme COR1.2, DNA and amino acid sequence determination and analysis, sequence comparison with codeinone reductase isoforms COR1.1, COR1.3, COR1.4, and COR-B, quantitative real-time PCR expression analysis. Isozyme COR1.2 exhibits lower expression levels compared to the other isozymes Papaver somniferum
isozyme COR1.3, DNA and amino acid sequence determination and analysis, sequence comparison with codeinone reductase isoforms COR1.2, COR1.1, COR1.4, and COR-B, quantitative real-time PCR expression analysis, recombinant coexpression of isozyme COR1.3 with thebaine 6-O-demethylase (T6ODM) in Saccharomyces cerevisiae strain CEN.PK fed with thebaine Papaver somniferum
isozyme COR1.4, DNA and amino acid sequence determination and analysis, sequence comparison with codeinone reductase isoforms COR1.2, COR1.3, COR1.1, and COR-B, quantitative real-time PCR expression analysis Papaver somniferum

Protein Variants

Protein Variants Comment Organism
A25V site-directed mutagenesis, the mutant shows a marginal increase in neopine formation compared to wild-type Papaver somniferum
A25V/E111D/T145S/S165C site-directed mutagenesis, the mutant shows a reduction in neopine formation compared to wild-type Papaver somniferum
E111D/T145S/S165C site-directed mutagenesis, the mutant shows a reduction in neopine formation compared to wild-type Papaver somniferum
F129L site-directed mutagenesis, the mutant of COR-B shows unaltered neopine formation compared to wild-type Papaver somniferum
K41N site-directed mutagenesis, the mutant of COR-B shows unaltered neopine formation compared to wild-type Papaver somniferum
L129F site-directed mutagenesis, the mutant shows a higher neopine yield compared to wild-type Papaver somniferum
additional information combinations and permutations of the three substitutions N41K, L129F and S279W do not produce a synergistic effect Papaver somniferum
additional information recombinant coexpression of isozyme COR-B with thebaine 6-O-demethylase (T6ODM) in Saccharomyces cerevisiae strain CEN.PK fed with thebaine, the strain expressing T6ODM and COR-B accumulates approximately 2fold more codeine and 10fold more neopine compared to wild-type Papaver somniferum
additional information recombinant coexpression of isozyme COR1.3 with thebaine 6-O-demethylase (T6ODM) in Saccharomyces cerevisiae strain CEN.PK fed with thebaine. In the recombinant strain, codeine and neopine accumulate to similar levels Papaver somniferum
additional information the COR1.4 single-substitution mutant A (A25V) results in a marginal increase in neopine formation, whereas the triple C (E111D), E (T145S) and F (S165C), and the quadruple A (A25V), C (E111D), E (T145S) and F (S165C), mutants result in higher reductions in neopine levels Papaver somniferum
N41K site-directed mutagenesis, the mutant shows a higher neopine yield compared to wild-type Papaver somniferum
S279W site-directed mutagenesis, the mutant shows a higher neopine yield compared to wild-type Papaver somniferum
V25A site-directed mutagenesis, the mutant of COR-B shows 2fold reduced neopine formation compared to wild-type Papaver somniferum
W279S site-directed mutagenesis, the mutant of COR-B shows 8fold reduced neopine formation compared to wild-type Papaver somniferum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state Michaelis-Menten kinetics Papaver somniferum
0.0117
-
codeinone pH 6.8, 30°C Papaver somniferum
0.0183
-
codeinone pH 6.8, 30°C Papaver somniferum
0.0298
-
codeine pH 9.0, 30°C Papaver somniferum
0.0312
-
codeine pH 9.0, 30°C Papaver somniferum
0.036
-
NADPH pH 6.8, 30°C Papaver somniferum
0.0462
-
NADP+ pH 9.0, 30°C Papaver somniferum
0.0648
-
NADPH pH 6.8, 30°C Papaver somniferum
0.0697
-
NADP+ pH 9.0, 30°C Papaver somniferum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
codeine + NADP+ Papaver somniferum
-
codeinone + NADPH + H+
-
r
additional information Papaver somniferum codeinone and morphinone are spontaneously converted to neopinone and neomorphinone, respectively. Latex protein extracts assayed for COR activity show the highest turnover of codeinone and morphinone to codeine and morphine, respectively. Codeine and morphine are also converted at reduced levels, whereas no conversion of either neopine or neomorphine is detected ?
-
-
morphine + NADP+ Papaver somniferum
-
morphinone + NADPH + H+
-
r
neomorphinone + NADPH + H+ Papaver somniferum
-
neomorphine + NADP+
-
ir
neopinone + NADPH + H+ Papaver somniferum
-
neopine + NADP+
-
ir

Organism

Organism UniProt Comment Textmining
Papaver somniferum A0A4P2SMY1 isozyme COR-B; chemotype Bea's Choice
-
Papaver somniferum Q9SQ67 isozyme COR1.4; chemotype Bea's Choice
-
Papaver somniferum Q9SQ68 isozyme COR1.3; chemotype Bea's Choice
-
Papaver somniferum Q9SQ69 isozyme COR1.2; chemotype Bea's Choice
-
Papaver somniferum Q9SQ70 isozyme COR1.1; chemotype Bea's Choice
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
codeine + NADP+
-
Papaver somniferum codeinone + NADPH + H+
-
r
additional information codeinone and morphinone are spontaneously converted to neopinone and neomorphinone, respectively. Latex protein extracts assayed for COR activity show the highest turnover of codeinone and morphinone to codeine and morphine, respectively. Codeine and morphine are also converted at reduced levels, whereas no conversion of either neopine or neomorphine is detected Papaver somniferum ?
-
-
additional information codeinone and morphinone are spontaneously converted to neopinone and neomorphinone, respectively Papaver somniferum ?
-
-
morphine + NADP+
-
Papaver somniferum morphinone + NADPH + H+
-
r
neomorphinone + NADPH + H+
-
Papaver somniferum neomorphine + NADP+
-
ir
neopinone + NADPH + H+
-
Papaver somniferum neopine + NADP+
-
ir

Synonyms

Synonyms Comment Organism
codeinone reductase
-
Papaver somniferum
COR
-
Papaver somniferum
COR-B
-
Papaver somniferum
COR1.1
-
Papaver somniferum
COR1.2
-
Papaver somniferum
COR1.3
-
Papaver somniferum
COR1.4
-
Papaver somniferum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
-
Papaver somniferum

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
additional information
-
addition of NADP+ and NADPH cofactors only a marginal effect on COR1.3 thermostability Papaver somniferum
additional information
-
addition of NADP+ and NADPH cofactors substantially increases the thermostability of COR-B Papaver somniferum
30 42 COR1.3 activity is maintained at 30-42°C, sharply reduced above 42°C and is not detected at 62°C Papaver somniferum
30 62 COR-B maintains activity from 30°C to 42°C and displays low activity at 62°C Papaver somniferum

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.015
-
codeine pH 9.0, 30°C Papaver somniferum
0.023
-
codeinone pH 6.8, 30°C Papaver somniferum
0.027
-
codeine pH 9.0, 30°C Papaver somniferum
0.04
-
codeinone pH 6.8, 30°C Papaver somniferum
0.044
-
NADP+ pH 9.0, 30°C Papaver somniferum
0.045
-
NADPH pH 6.8, 30°C Papaver somniferum
0.06
-
NADPH pH 6.8, 30°C Papaver somniferum
0.067
-
NADP+ pH 9.0, 30°C Papaver somniferum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.8
-
reduction of codeinone to codeine Papaver somniferum
9
-
oxidation of codeine to codeinone Papaver somniferum

Cofactor

Cofactor Comment Organism Structure
NADP+
-
Papaver somniferum
NADPH
-
Papaver somniferum

General Information

General Information Comment Organism
evolution deduction and calculation of sequences of codeinone reductase isoforms COR1.1, COR1.2, COR1.3, COR1.4, and COR-B, overview. In 3-h assays using codeine and NADP+ as substrates, isozyme COR-B yields the most neopine, followed by COR1.4, COR1.2, COR1.1, and COR1.3. The four residues (V25, K41, F129 and W279) responsible for the differential function of COR-B, compared with COR1.1-1.4, are predominant among COR isoforms in various opium poppy chemotypes Papaver somniferum
metabolism codeinone reductase (COR) catalyzes the reversible NADPH-dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). In a parallel pathway involving 3-O-demethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, the formation of neomorphine by COR is irreversible Papaver somniferum
additional information COR structure homology modeling using chain A of the crystal structure of CHR complexed with NADPH (PDB ID 1ZGD) as a template Papaver somniferum
additional information COR structure homology modeling using chain A of the crystal structure of CHR complexed with NADPH (PDB ID 1ZGD) as a template. Structure-function relationships of isozymes COR1.3 and COR-B, comparisons, overview Papaver somniferum
physiological function codeinone reductase (COR) catalyzes the reversible NADPH-dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). It also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3-O-demethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine Papaver somniferum

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.197
-
codeinone pH 6.8, 30°C Papaver somniferum
0.503
-
codeine pH 9.0, 30°C Papaver somniferum
0.631
-
NADP+ pH 9.0, 30°C Papaver somniferum
0.865
-
codeine pH 9.0, 30°C Papaver somniferum
0.925
-
NADPH pH 6.8, 30°C Papaver somniferum
1.25
-
NADPH pH 6.8, 30°C Papaver somniferum
1.45
-
NADP+ pH 9.0, 30°C Papaver somniferum
2.19
-
codeinone pH 6.8, 30°C Papaver somniferum