10020-96-9Relevant articles and documents
The Oxidation of Benzaldehyde to Benzoic Acid Catalysed by Cyclo-, and its Implications for the Catalytic Assymmetric Addition of HCN to Aldehydes
Hogg, David J.P.,North, Michael,Stokoe, Robert B.,Teasdale, William G.
, p. 1553 - 1558 (1993)
Key Words: cyclo-; Benzaldehyde; Oxidation; Asymmetric Hydrocyanation; Mechanism The cyclic dipeptide cyclo- is found to catalyse the oxidation of benzaldehyde to benzoic acid.A mechanism is proposed both for this reactio
Asymmetric Cyanohydrin Synthesis catalysed by a Synthetic Cyclic Dipeptide
Oku, Jun-ichi,Inoue, Shohei
, p. 229 - 230 (1981)
Asymmetric addition of hydrogen cyanide to benzaldehyde catalysed by cyclo(L-phenylalanyl-L-histidine) gave the highest optical yield ever obtained.
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Krieble
, (1915)
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Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases
Devamani, Titu,Rauwerdink, Alissa M.,Lunzer, Mark,Jones, Bryan J.,Mooney, Joanna L.,Tan, Maxilmilien Alaric O.,Zhang, Zhi-Jun,Xu, Jian-He,Dean, Antony M.,Kazlauskas, Romas J.
, p. 1046 - 1056 (2016)
Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ～100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.
Asymmetric synthesis of an (R)-cyanohydrin using enzymes entrapped in lens-shaped gels.
Groeger,Capan,Barthuber,Vorlop
, p. 1969 - 1972 (2001)
[structure: see text] A novel synthesis of (R)-cyanohydrins is described which is based on the use of cross-linked and subsequently poly(vinyl alcohol)-entrapped (R)-oxynitrilases. These immobilized lens-shaped biocatalysts have a well-defined macroscopic
Hydroxynitrile Lyase of Wild Apricot (Prunus armeniaca L.): Purification, Characterization and Application in Synthesis of Enantiopure Mandelonitrile
Asif, Mohammad,Bhalla, Tek Chand
, p. 1118 - 1127 (2016)
Abstract: Hydroxynitrile lyases (HNLs) are increasingly finding application in synthesis of enantiomerically pure cyanohydrins. Cyanohydrins are important intermediates in the production of pharmaceuticals and agrochemicals. In the present studies seeds of wild apricot (Prunus armeniaca L.) have emerged as potential source of hydroxynitrile lyase. The HNL of wild apricot (ParsHNL) was purified 8.1 fold and 18.2?% yield with a specific activity of 141 units?mg?1 protein. The SDS-PAGE of the enzyme revealed that it consists of subunits of 40 and 37?kDa. However, the molecular weight of holoenzyme was assessed to be 360?kDa. The enzyme showed maximum activity in 0.1?M sodium-citrate buffer having pH 4.75 at 25?°C. Thermostability studies revealed that this HNL showed activity up to 70?°C temperature and quite stable up to 50?°C. Activation energy of ParsHNL was calculated to be 37.83?kJ?mol?1. This enzyme has Km of 3.76?mM, Vmax of 188.4?μmol?mg?1 min?1 and kcat of 1130.4?s?1 using mandelonitrile as substrate while for reverse reaction using benzaldehyde as substrate it showed Km of 16.1?mM, Vmax of 7.21?μmol?mg?1 min?1 and kcat of 43.3?s?1. Synthesis of mandelonitrile was carried out using ParsHNL and finally 8.88?mmole (1.184?g) of mandelonitrile was recovered which corresponded to 89?% molar conversion with 96?% ee for R-mandelonitrile. The yield of mandelonitrile was 411?μmol?mg?1h?1. These results indicated that ParsHNL has very high potential for synthesis of cyanohydrins and can be used for the production of enantiopure cyanohydrins. Graphical Abstract: [Figure not available: see fulltext.]
Sol-Gel Glass with Enantioselective Catalytic Activity
Shvo, Youval,Becker, Yigal,Gal, Meir
, p. 2719 - 2720 (1994)
Cyclo entrapped in a silicon based sol-gel glass matrix induces catalytic hydrocyanation of benzaldehyde to (R)-mandelonitrile with e.e. >= 94percent.
Straightforward enzymatic process based on HNL CLEA-catalysis towards cyanohydrin derivatives
Cabirol, Fabien L.,Lim, Angela E. C.,Hanefeld, Ulf,Sheldon, Roger A.
, p. 114 - 118 (2010)
An efficient enzymatic process based on HNL-CLEA catalysis in buffer-saturated organic media was developed to limit the amount of overall waste generated and the number of safety issues incurred by handling HCN-containing waste. Starting from benzaldehyde as a model substrate, (R)- and (S)-mandelonitrile can be obtained under these reaction conditions without an extraction step being required. The crude cyanohydrin intermediate was sufficiently pure to be used as starting material in a second step towards a range of derivatives.
Activity and enantioselectivity of the hydroxynitrile lyase MeHNL in dry organic solvents
Paravidino, Monica,Sorgedrager, Menno J.,Orru, Romano V. A.,Hanefeld, Ulf
, p. 7596 - 7604 (2010)
Water concentration affects both the enantioselectivity and activity of enzymes in dry organic media. Its influence has been investigated using the hydrocyanation of benzaldehyde catalyzed by hydroxynitrile lyase cross-linked enzyme aggregate (A/eHNL-CLEA) as a model reaction. The enzyme displayed higher enantioselectivity at higher water concentration, thus suggesting a positive effect of enzyme flexibility on selectivity. The activity increased on reducing the solvent water content, but drastic dehydration of the enzyme resulted in a reversible loss of activity.
Comprehensive Step-by-Step Engineering of an (R)-Hydroxynitrile Lyase for Large-Scale Asymmetric Synthesis
Glieder, Anton,Weis, Roland,Skranc, Wolfgang,Poechlauer, Peter,Dreveny, Ingrid,Majer, Sandra,Wubbolts, Marcel,Schwab, Helmut,Gruber, Karl
, p. 4815 - 4818 (2003)
A custom-made enzyme: The gene and protein sequence of a new (R)-hydroxynitrile lyase from Prunus amygdalus was cloned and engineered for recombinant production on a large scale. The enzyme is stable and active at low pH values. A rationally designed acti
Immobilized Baliospermum montanum hydroxynitrile lyase catalyzed synthesis of chiral cyanohydrins
Jangir, Nisha,Padhi, Santosh Kumar
, p. 32 - 40 (2019)
Hydroxynitrile lyase (HNL) catalyzed enantioselective C–C bond formation is an efficient approach to synthesize chiral cyanohydrins which are important building blocks in the synthesis of a number of fine chemicals, agrochemicals and pharmaceuticals. Immobilization of HNL is known to provide robustness, reusability and in some cases also enhances activity and selectivity. We optimized the preparation of immobilization of Baliospermium montanum HNL (BmHNL) by cross linking enzyme aggregate (CLEA) method and characterized it by SEM. Optimization of biocatalytic parameters was performed to obtain highest % conversion and ee of (S)-mandelonitrile from benzaldehyde using CLEA-BmHNL. The optimized reaction parameters were: 20 min of reaction time, 7 U of CLEA-BmHNL, 1.2 mM substrate, and 300 mM citrate buffer pH 4.2, that synthesized (S)-mandelonitrile in ～99% ee and ～60% conversion. Addition of organic solvent in CLEA-BmHNL biocatalysis did not improve in % ee or conversion of product unlike other CLEA-HNLs. CLEA-BmHNL could be successfully reused for eight consecutive cycles without loss of conversion or product formation and five cycles with a little loss in enantioselectivity. Eleven different chiral cyanohydrins were synthesized under optimal biocatalytic conditions in up to 99% ee and 59% conversion, however the % conversion and ee varied for different products. CLEA-BmHNL has improved the enantioselectivity of (S)-mandelonitrile synthesis compared to the use of purified BmHNL. Nine aldehydes not tested earlier with BmHNL were converted into their corresponding (S)-cyanohydrins for the first time using CLEA-BmHNL. Among the eleven (S)-cyanohydrins syntheses reported here, eight of them have not been synthesized by any CLEA-HNL. Overall, this study showed preparation, characterization of a stable, robust and recyclable biocatalyst i.e. CLEA-BmHNL and its biocatalytic application in the synthesis of different (S)-aromatic cyanohydrins.
Partial purification and immobilization of a new (R)-hydroxynitrile lyase from seeds of Prunus pseudoarmeniaca
Tuekel, S. Seyhan,Yildirim, Deniz,Alagoez, Dilek,Alptekin, Oezlem,Yuecebilgi, Guezide,Bilgin, Ramazan
, p. 161 - 165 (2010)
Hydroxynitrile lyase (HNL) from seeds of Prunus pseudoarmeniaca was partially purified by (NH4)2SO4 fractionation and covalently immobilized onto Eupergit C and Eupergit C 250 L. The percentages of bound protein per gram o
Temperature-triggered switchable helix-helix inversion of poly(phenylacetylene) bearing L-valine ethyl ester pendants and its chiral recognition ability
Zhou, Yanli,Zhang, Chunhong,Qiu, Yuan,Liu, Lijia,Yang, Taotao,Dong, Hongxing,Satoh, Toshifumi,Okamoto, Yoshio
, (2016)
A phenylacetylene containing the L-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh4) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N′-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature. Even after six cycles of the heating-cooling treatment, the helix sense of the PPAA-Val's backbone was still switchable without loss of the CD intensity. The PPAA-Val was then coated on silica gel particles to produce novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high chiral recognition ability for racemic mandelonitrile (α = 2.18) and racemic trans-N,N′-diphenylcyclohexane-1,2-dicarboxamide (α = 2.60). Additionally, the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO) accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val-H had the same L-valine ethyl ester pendants as its cis-isomer PPAA-Val, it showed no chiral recognition. It was concluded that the one-handed helical cis-polyene backbone of PPAA-Val plays an important role in the chiral recognition ability.
Synthesis of enantiomerically pure (S)-mandelic acid using an oxynitrilase-nitrilase bienzymatic cascade: A nitrilase surprisingly shows nitrile hydratase activity
Mateo, Cesar,Chmura, Andrzej,Rustler, Sven,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
, p. 320 - 323 (2006)
Benzaldehyde was converted into enantiomerically pure (S)-mandelic acid by sequential HCN addition and hydrolysis in the presence of a cross-linked enzyme aggregate composed of the (S)-selective oxynitrilase from Manihot esculenta and the non-selective recombinant nitrilase from Pseudomonas fluorescens EBC 191. Surprisingly, (S)-mandelic amide was formed in large amounts. It was shown, in separate experiments, that the nitrilase hydrolyses (S)-mandelonitrile into an approx. equimolar mixture of acid and amide, whereas with the (R)-enantiomer only 10% of amide was formed.
Probing batch and continuous flow reactions in organic solvents:Granulicella tundricolahydroxynitrile lyase (GtHNL)
Coloma, José,Guiavarc'h, Yann,Hagedoorn, Peter-Leon,Hanefeld, Ulf
, p. 3613 - 3621 (2020)
Granulicella tundricolahydroxynitrile lyase (GtHNL) is a manganese dependent cupin which catalyses the enantioselective synthesis of (R)-cyanohydrins. TheGtHNL triple variant A40H/V42T/Q110H, previously reported to exhibit a high activity and stability, w
R-hydroxynitrile lyase from the cyanogenic millipede, Chamberlinius hualienensis—A new entry to the carrier protein family Lipocalines
Motojima, Fumihiro,Izumi, Atsushi,Nuylert, Aem,Zhai, Zhenyu,Dadashipour, Mohammad,Shichida, Sayaka,Yamaguchi, Takuya,Nakano, Shogo,Asano, Yasuhisa
, p. 1679 - 1695 (2021)
Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrin into cyanide and the corresponding aldehyde or ketone. Moreover, they catalyze the synthesis of cyanohydrin in the reverse reaction, utilized in industry for preparation of enantiomeric pure pharmaceutical ingredients and fine chemicals. We discovered a new HNL from the cyanogenic millipede, Chamberlinius hualienensis. The enzyme displays several features including a new primary structure, high stability, and the highest specific activity in (R)-mandelonitrile ((R)-MAN) synthesis (7420 U·mg?1) among the reported HNLs. In this study, we elucidated the crystal structure and reaction mechanism of natural ChuaHNL in ligand-free form and its complexes with acetate, cyanide ion, and inhibitors (thiocyanate or iodoacetate) at 1.6, 1.5, 2.1, 1.55, and 1.55?? resolutions, respectively. The structure of ChuaHNL revealed that it belongs to the lipocalin superfamily, despite low amino acid sequence identity. The docking model of (R)-MAN with ChuaHNL suggested that the hydroxyl group forms hydrogen bonds with R38 and K117, and the nitrile group forms hydrogen bonds with R38 and Y103. The mutational analysis showed the importance of these residues in the enzymatic reaction. From these results, we propose that K117 acts as a base to abstract a proton from the hydroxyl group of cyanohydrins and R38 acts as an acid to donate a proton to the cyanide ion during the cleavage reaction of cyanohydrins. The reverse mechanism would occur during the cyanohydrin synthesis. (Photo: Dr. Yuko Ishida). Databases: Structural data are available in PDB database under the accession numbers 6JHC, 6KFA, 6KFB, 6KFC, and 6KFD.
A study on increasing enzymatic stability and activity of Baliospermum montanum hydroxynitrile lyase in biocatalysis
Jangir, Nisha,Preeti,Padhi, Santosh Kumar
, p. 78 - 89 (2020)
HNL catalysis is usually carried out in a biphasic solvent and at low pH to suppress the non-enzymatic synthesis of racemic cyanohydrins. However, enzyme stability under these conditions remain a challenge. We have investigated the effect of different biocatalytic parameters, i.e., pH, temperature, buffer concentrations, presence of stabilizers, organic solvents, and chemical additives on the stability of Baliospermum montanum hydroxynitrile lyase (BmHNL). Unexpectedly, glycerol (50 mg/mL) added BmHNL biocatalysis had produced >99% of (S)-mandelonitrile from benzaldehyde, while without glycerol it is 54% ee. Similarly, BmHNL had converted 3-phenoxy benzaldehyde and 3,5-dimethoxy benzaldehyde, to their corresponding cyanohydrins in the presence of glycerol. Among the different stabilizers added to BmHNL at low pH, 400 mg/mL of sucrose had increased enzyme's half-life more than fivefold. BmHNL's stability study showed half-lives of 554, 686, and 690 h at its optimum pH 5.5, temperature 20 °C, buffer concentration, i.e., 100 mM citrate-phosphate pH 5.5. Addition of benzaldehyde as inhibitor, chemical additives, and the presence of organic solvents have decreased both the stability and activity of BmHNL, compared to their absence. Secondary structural study by CD-spectrophotometer showed that BmHNL's structure is least affected in the presence of different organic solvents and temperatures.
Development of a family of β-amino alcohol ligands with two stereocenters for highly efficient enantioselective trimethylsilylcyanation of aldehydes
You,Gau,Choi
, p. 1963 - 1964 (2000)
The asymmetric addition of Me3SiCN to aldehydes catalyzed by titanium(IV) complexes of N-sulfonylated derivatives of β-amino alcohols gave excellent ee's up to 96% ee.
Enantioselective formation of mandelonitrile acetate - Investigation of a dynamic kinetic resolution
Li, Yu-Xin,Straathof, Adrie J.J.,Hanefeld, Ulf
, p. 739 - 743 (2002)
Investigations into the separate reactions of a dynamic kinetic resolution and the combined reactions revealed that the overall sequence is highly susceptible to the water content of the reaction mixture. While the racemization and formation of mandelonitrile as well as its kinetic resolution proceeded rapidly when performed independently, the dynamic kinetic resolution was severely hampered by the undesired formation of acetic acid during the reaction. The utilization of drying reagents and neutralizing agents in order to suppress the formation of acetic acid or its consequences were investigated.
Enzyme engineering improves catalytic efficiency and enantioselectivity of hydroxynitrile lyase for promiscuous retro-nitroaldolase activity
Akif, Mohd.,Gilani, Rubina,Kumar Padhi, Santosh,Lata, Surabhi,Rai, Nivedita,Sreenivasa Rao, D. H.,Vishnu Priya, Badipatla
, (2022/01/11)
Protein engineering to improve promiscuous catalytic activity is important for biocatalytic application of enzymes in green synthesis. We uncovered the significance of binding site residues in Arabidopsis thaliana hydroxynitrile lyase (AtHNL) for promiscuous retro-nitroaldolase activity. Engineering of AtHNL has improved enantioselective retro-nitroaldolase activity, a synthetically important biotransformation, for the production of enantiopure β-nitroalcohols having absolute configuration opposite to that of the stereopreference of the HNL. The variant F179A has shown ～ 12 fold increased selectivity towards the retro-nitroaldol reaction over cyanogenesis, the natural activity of the parent enzyme. Screening of the two saturation libraries of Phe179 and Tyr14 revealed several variants with higher kcat, while F179N showed ～ 2.4-fold kcat/Km than the native enzyme towards retro-nitroaldol reaction. Variants F179N, F179M, F179W, F179V, F179I, Y14L, and Y14M have shown > 99% ee in the preparation of (S)-2-nitro-1-phenylethanol (NPE) from the racemic substrate, while F179N has shown the E value of 138 vs. 81 by the wild type. Our molecular docking and dynamics simulations (MDS) studies results provided insights into the molecular basis of higher enantioselectivity by the F179N toward the retro-nitroaldolase activity than the other mutants. Binding energy calculations also showed the higher negative binding free energy in the case of F179N-(R)-NPE compared to other complexes that support our experimental low Km by the F179N for NPE. A plausible retro-nitroaldol reaction mechanism was proposed based on the MDS study of enzyme-substrate interaction.
Structure-Guided Tuning of a Hydroxynitrile Lyase to Accept Rigid Pharmaco Aldehydes
Hong, Ran,Li, Fu-Long,Lin, Guo-Qiang,Lin, Zuming,Xu, Jian-He,Yu, Hui-Lei,Zheng, Yu-Cong
, p. 5757 - 5763 (2020/06/09)
The chiral vicinal C-O/C-N bifunctional groups generated from enzymatic hydrocyanation represents a useful methodology. However, construction of the pharmacophore of β2-adrenoreceptor agonists with this method remains a great challenge because of complete racemization of the benzylic alcohol during deprotection of the acetal groups. In this study, structure-guided redesign of a hydroxynitrile lyase originating from Prunus communis (PcHNL5) enables a highly enantioselective hydrocyanation of rigid benzo-ketal aldehyde which was proved to be resistant against racemization during the deprotection step, with dramatically improved productivity (>95% conversion vs 2-adrenoreceptor agonist, in an optically pure form (>99% ee) with an overall yield of 54%, which is the highest value reported.
