The enzyme participates in an alternative pathway for biosynthesis of (R)-pantothenate (vitamin B5). This entry covers enzymes whose stereo specificity for NADP+ is not known. cf. EC 1.1.1.168 2-dehydropantolactone reductase (Re-specific) and EC 1.1.1.214, 2-dehydropantolactone reductase (Si-specific).
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding
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SYSTEMATIC NAME
IUBMB Comments
(R)-pantolactone:NADP+ oxidoreductase
The enzyme participates in an alternative pathway for biosynthesis of (R)-pantothenate (vitamin B5). This entry covers enzymes whose stereo specificity for NADP+ is not known. cf. EC 1.1.1.168 2-dehydropantolactone reductase (Re-specific) and EC 1.1.1.214, 2-dehydropantolactone reductase (Si-specific).
recombinant CorCPR exhibited a high catalytic activity for the synthesis of (R)-pantolactone ((R)-PL) from 2-dehydropantolactone (KPL). The activity assay is performed using purified CorCPR and crude recombinant GDH in a single batch reaction. GDH is used to complete the enzyme-coupled NADPH regeneration system. CPR-01 form Candida orthopsilosis Co 90-125 exhibits excellent enantioselectivity (enantiomeric excess of over 99%). CorCPR exhibits the highest activity and stereoselectivity toward KPL
recombinant CorCPR exhibited a high catalytic activity for the synthesis of (R)-pantolactone ((R)-PL) from 2-dehydropantolactone (KPL). The activity assay is performed using purified CorCPR and crude recombinant GDH in a single batch reaction. GDH is used to complete the enzyme-coupled NADPH regeneration system. CPR-01 form Candida orthopsilosis Co 90-125 exhibits excellent enantioselectivity (enantiomeric excess of over 99%). CorCPR exhibits the highest activity and stereoselectivity toward KPL
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
enzyme CduCPR shows high catalytic activity and stereoselectivity using 2-dehydropantolactone (KPL) as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone is reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess within 2.0 h by the purified recombinant enzyme
the aldo-keto reductase (AKR) can catalyze ketopantoyl lactone to optically active (R)-pantolactone. A putative catalytic mechanism is proposed that Tyr63 acts as a general acid. No activity of recombinant CorCPR with typical AKR substrates such as p-nitrobenzaldehyde. Other alpha-oxoesters are not the optimal substrates of CorCPR due to the relatively low activities and low stereoselectivities
the aldo-keto reductase (AKR) can catalyze ketopantoyl lactone to optically active (R)-pantolactone. A putative catalytic mechanism is proposed that Tyr63 acts as a general acid. No activity of recombinant CorCPR with typical AKR substrates such as p-nitrobenzaldehyde. Other alpha-oxoesters are not the optimal substrates of CorCPR due to the relatively low activities and low stereoselectivities
NADPH is embedded in the coenzyme binding groove in an extended conformation, and the nicotinamide ring positioned at the bottom of the substrate binding cavity. The adenosine 2'-phosphate group is bound to the side chains of Lys28, Ser263 and Arg267 of CorCPR
docking analysis and structure homology modeling of CorCPR, the crystal structure of CPR-C2 from Candida parapsilosis strain IFO 0708 (PDB ID 3VXG, resolution 1.7 A) is used as the model structure, overview. KPL is docked into the substrate binding pocket. The model predicts that the C3 carbonyl oxygen of KPL forms hydrogen bond with the side chains of Tyr63, and the alpha-amino group of Thr27 also forms a hydrogen bond with C2 carbonyl oxygen. The catalytic tetrads of CorCPR are Asp58, Tyr63, Lys88 and His125. Tyr63 acts as a general acid, and His125 facilitates proton donation, the phenolic hydroxy group of Tyr63 provide general acid catalytic assistance to carbonyl group of KPL, and residues Asp 58 and Tys88 are responsible for the hydrogen transfer. The stereospecificity of CorCPR is respected to the pro-R hydrogen at C4 of the nicotinamide ring and the pseudo re-side attack of the hydride on the carbonyl group. In addition, the formation of hydrogen bond between Thr27 and the C2 carbonyl oxygen of KPL plays an important role in substrate recognition
docking analysis and structure homology modeling of CorCPR, the crystal structure of CPR-C2 from Candida parapsilosis strain IFO 0708 (PDB ID 3VXG, resolution 1.7 A) is used as the model structure, overview. KPL is docked into the substrate binding pocket. The model predicts that the C3 carbonyl oxygen of KPL forms hydrogen bond with the side chains of Tyr63, and the alpha-amino group of Thr27 also forms a hydrogen bond with C2 carbonyl oxygen. The catalytic tetrads of CorCPR are Asp58, Tyr63, Lys88 and His125. Tyr63 acts as a general acid, and His125 facilitates proton donation, the phenolic hydroxy group of Tyr63 provide general acid catalytic assistance to carbonyl group of KPL, and residues Asp 58 and Tys88 are responsible for the hydrogen transfer. The stereospecificity of CorCPR is respected to the pro-R hydrogen at C4 of the nicotinamide ring and the pseudo re-side attack of the hydride on the carbonyl group. In addition, the formation of hydrogen bond between Thr27 and the C2 carbonyl oxygen of KPL plays an important role in substrate recognition
apoenzyme and in complex with NADPH, sitting drop vapor diffusion method, using 0.1 M TrisHCl (pH 8.1) and 23% (w/v) polyethylene glycol 3350, at 20°C
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
an effective biocatalytic cascade was developed by encapsulating a conjugated polyketone reductase (CPR), glucose dehydrogenase (GDH) and the coenzyme NADP+ in organic-inorganic hybrid nanoflowers (hNFs) for the asymmetric reduction of oxopantolactone (KPL) to synthesize (R)-(-)-pantolactone ((R)-PL). When CduCPR and TgGDH are confined in the sodium alginate (SA)-coated hNFs [CduCPR/TgGDH-Ca3(PO4)2], both of them have excellent reusability and high stability. The SA-coated hNF reactor successfully catalyzes the asymmetric synthesis of (R)-PL, which exhibits satisfactory stereoselectivity and promotes reusability in repeated batches. The SA coating functioned to competently immobilize the coenzyme NADP+ on the CduCPR/TgGDH-Ca3(PO4)2 hNFs, which maintains the maximum bioactivity to synthesize (R)-PL without exogenous coenzyme addition. Method development, optimization, and evaluation, overview
the enzyme has a potential application in the asymmetric synthesis of optically active (R)-pantothenate, synthetic method of (R)-pantothenate production through the stereoselective reduction of oxopantoyl lactone (KPL) by aldo-keto reductase (AKR). (R)-Pantolactone (PL) is a key chiral building block for the synthesis of calcium (R)-pantothenate (vitamin B5), (R)-panthenol, and (R)-pantetheine, which are used as food and feed additives, as well as ingredients in pharmaceutical and cosmetic compositions
the enzyme has a potential application in the asymmetric synthesis of optically active (R)-pantothenate, synthetic method of (R)-pantothenate production through the stereoselective reduction of oxopantoyl lactone (KPL) by aldo-keto reductase (AKR). (R)-Pantolactone (PL) is a key chiral building block for the synthesis of calcium (R)-pantothenate (vitamin B5), (R)-panthenol, and (R)-pantetheine, which are used as food and feed additives, as well as ingredients in pharmaceutical and cosmetic compositions
Kataoka, M.; Delacruz-Hidalgo, A.R.G.; Akond, M.A.; Sakuradani, E.; Kita, K.; Shimizu, S.
Gene cloning and overexpression of two conjugated polyketone reductases, novel aldo-keto reductase family enzymes, of Candida parapsilosis. Investigation of hydroxamic acids as laccase-mediators for pulp bleaching
Structure of conjugated polyketone reductase from Candida parapsilosis IFO 0708 reveals conformational changes for substrate recognition upon NADPH binding
Cheng, P.; Wang, J.; Wu, Y.; Jiang, X.; Pei, X.; Su, W.
Recombinant expression and molecular insights into the catalytic mechanism of an NADPH-dependent conjugated polyketone reductase for the asymmetric synthesis of (R)-pantolactone
Discovery of a new NADPH-dependent aldo-keto reductase from Candida orthopsilosis catalyzing the stereospecific synthesis of (R)-pantolactone by genome mining
J. Biotechnol.
291
26-34
2019
Candida orthopsilosis, Candida orthopsilosis Co 90-125
Cheng, P.; Tang, M.; Chen, Z.; Liu, W.; Jiang, X.; Pei, X.; Su, W.
Dual-enzyme and NADPH co-embedded organic-inorganic hybrid nanoflowers prepared using biomimetic mineralization for the asymmetric synthesis of ( R)-(-)-pantolactone