1.14.20.3: (5R)-carbapenem-3-carboxylate synthase
This is an abbreviated version!
For detailed information about (5R)-carbapenem-3-carboxylate synthase, go to the full flat file.
Word Map on EC 1.14.20.3
Reaction
Synonyms
carbapenem synthase, CarC
ECTree
1.14.20.3 (5R)-carbapenem-3-carboxylate synthaseAdvanced search results
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Substrates Products on EC 1.14.20.3 - (5R)-carbapenem-3-carboxylate synthase
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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
(3R,5R)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
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activity in presence of ascorbate is 22% compared to the activity with the natural substrate (3S,5S)-carbapenam-3-carboxylate, activity in absence of ascorbate is 86% compared to the activity with the natural substrate (3S,5S)-carbapenam-3-carboxylate in presence of ascorbate
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-
?
(3R,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
activity in presence of ascorbate is less than 2% compared to the activity with the natural substrate (3S,5S)-carbapenam, activity in absence of ascorbate is 40% compared to the activity with the natural substrate (3S,5S)-carbapenam in presence of ascorbate
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-
?
(3S,5R)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
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activity in presence of ascorbate is 76% compared to the activity with the natural substrate (3S,5S)-carbapenam-3-carboxylate, activity in absence of ascorbate is 7% compared to the activity with the natural substrate (3S,5S)-carbapenam-3-carboxylate in presence of ascorbate
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-
?
(3S,5S)-carbapen-2-am-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
(3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
(3S,5S)-carbapen-2-am-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
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-
-
-
?
(3S,5S)-carbapen-2-am-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
the enzyme is involved in the biosynthesis of (5R)-carbapen-2-em-3-carboxylic acid the simplest structurally among the naturally occurring carbapenem beta-lactam antibiotics
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-
?
(3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
-
-
-
?
(3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
natural substrate. Activity with in absence of ascorbate is 2% compared to the activity in presence of ascorbate
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-
?
(3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
the contrathermodynamic epimerization of (3S,5S)-carbapenam-3-carboxylate to (3S,5R)-carbapenam-3-carboxylate is coupled at least to the binding of 2-oxoglutarate and it is probably coupled to the reduction of molecular oxygen and proceeds by way of radical abstraction at C-5. The presumed Fe(IV)=O species formed in these processes is required to drive the subsequent desaturation process
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-
?
(3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2
(5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
-
quantum mechanics/molecular mechanics calculations uncover the reaction mechanism of CarC. The dioxygen binding site on metal is analyzed and it is identified that the Fe(IV)-oxo species has two potential orientations with the oxo group trans to either His101 or His251. The former is energetically unstable, which can rapidly isomerize into the latter by rotation of the oxo group. Arg279 plays important roles in regulating the dioxygen binding and assisting the isomerization of Fe(IV)-oxo species. The calculation results clearly support the stepwise C5-epimerization and C2/3-desaturation processes, involving two complete oxidative cycles. The epimerization process converts (3S,5S)-carbapenam to the initial product (3S,5R)-carbapenam, undergoing H5 atom abstraction by Fe(IV)-O species, inversion of the C5-radical, and reconstitution of the inverted C5-H bond by Tyr165. In the desaturation process, (3S,5R)-carbapenam rebinds the CarC active site with a new orientation different from what (3S,5S)-carbapenam does in the epimerization. In addition, the desaturation across C2-C3 occurs without involving any active site residue other than the Fe(IV)-O center. Whereas Tyr165 is not involved in the desaturation reaction, it plays a key role in binding (3S,5R)-carbapenam. (3S,5R)-Carbapenam is a substrate superior to its epimer (3S,5S)-carbapenam for CarC to produce (5R)-carbapenem by efficient desaturation. In addition, the substrate hydroxylations compete with the target epimerization and desaturation reaction
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