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(S)-hydroxynitrile lyase

December 15, 2023

(S)-hydroxynitrile lyase (EC 4.1.2.47, (S)-cyanohydrin producing hydroxynitrile lyase, (S)-oxynitrilase, (S)-HbHNL, (S)-MeHNL, hydroxynitrile lyase, oxynitrilase, HbHNL, MeHNL, (S)-selective hydroxynitrile lyase, (S)-cyanohydrin carbonyl-lyase (cyanide forming), hydroxynitrilase) is an enzyme with systematic name (S)-cyanohydrin lyase (cyanide forming).[1][2][3][4][5][6][7][8][9][10] This enzyme catalyses the interconversion between cyanohydrins and the carbonyl compounds derived from the cyanohydrin with free cyanide, as in the following two chemical reactions:

  • an aliphatic (S)-hydroxynitrile an aliphatic aldehyde or ketone + cyanide
  • an aromatic (S)-hydroxynitrile an aromatic aldehyde + cyanide
(S)-hydroxynitrile lyase
Identifiers
EC no.4.1.2.47
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins

In nature, the liberation of cyanide serves as a defense mechanism against herbivores and microbial attack in plants.[11] Hydroxynitrile lyases of the α/β hydrolase fold are closely related to esterases. All members of the α/β hydrolase fold contain a conserved catalytic triad (nucleophile-histidine-aspartate).[12] The nucleophile in this case is a serine. In contrast to esterases, serine proteases, lipases and other enzymes in this family, the nucleophile in hydroxynitrile lyases functions as a proton acceptor.[13] Key amino acid residues in this reaction are the lysine at position 236 and the threonine at position 11.[14] Lys236 helps to orient the substrate while Thr11 serves to block the oxyanion hole that would convert the enzyme into an esterase.[15]

Commonly studied (S)-selective hydroxynitrile lyases include MeHNL from Manihot esculenta and HbHNL from Hevea brasiliensis. (R)-selective hydroxynitrile lyases have also been found to exist in Arabidopsis thaliana (AtHNL). AtHNL is thought to catalyze this reaction by a different mechanism.[16]

Not all hydroxynitrile lyases belong to the α/β hydrolase family. PaHNL (Prunus amygdalus), (R)-selective like AtHNL, uses a flavin cofactor to catalyze cyanogenesis.[17]

Natural Substrates of Hydroxynitrile Lyases edit

Acetone cyanohydrin has been determined to be the natural substrate of HbHNL, though HbHNL also shows activity with mandelonitrile, the natural substrate of PaHNL. The cleavage of mandelonitrile into benzaldehyde and cyanide is what produces the characteristic amaretto smell of almonds.[18] The natural substrate of AtHNL is unknown as no cyanohydrins have been detected in Arabidopis thaliana.

Unnatural Substrates edit

In addition to cyanohydrin cleavage, HNLs have been found to catalyze the nitroaldol reaction at low levels.[19]

References edit

  1. ^ Förster, S.; Roos, J.; Effenberger, F.; Wajant, H.; Sprauer, A. (1996). "The first recombinant hydroxynitrile lyase and its application in the synthesis of (S)-cyanohydrins". Angew. Chem. Int. Ed. 35 (4): 437–439. doi:10.1002/anie.199604371.
  2. ^ Bühler, H.; Effenberger, F.; Förster, S.; Roos, J.; Wajant, H. (2003). "Substrate specificity of mutants of the hydroxynitrile lyase from Manihot esculenta". ChemBioChem. 4 (2–3): 211–216. doi:10.1002/cbic.200390033. PMID 12616635.
  3. ^ Semba, H.; Dobashi, Y.; Matsui, T. (2008). "Expression of hydroxynitrile lyase from Manihot esculenta in yeast and its application in (S)-mandelonitrile production using an immobilized enzyme reactor". Biosci. Biotechnol. Biochem. 72 (6): 1457–1463. doi:10.1271/bbb.70765. PMID 18540112.
  4. ^ Avi, M.; Wiedner, R.M.; Griengl, H.; Schwab, H. (2008). "Improvement of a stereoselective biocatalytic synthesis by substrate and enzyme engineering: 2-hydroxy-(4′-oxocyclohexyl)acetonitrile as the model". Chemistry: A European Journal. 14 (36): 11415–11422. doi:10.1002/chem.200800609. PMID 19006143.
  5. ^ von Langermann, J.; Guterl, J.K.; Pohl, M.; Wajant, H.; Kragl, U. (2008). "Hydroxynitrile lyase catalyzed cyanohydrin synthesis at high pH-values". Bioprocess Biosyst. Eng. 31 (3): 155–161. doi:10.1007/s00449-008-0198-4. PMID 18204865.
  6. ^ Schmidt, A.; Gruber, K.; Kratky, C.; Lamzin, V.S. (2008). "Atomic resolution crystal structures and quantum chemistry meet to reveal subtleties of hydroxynitrile lyase catalysis". J. Biol. Chem. 283 (31): 21827–21836. doi:10.1074/jbc.m801056200. PMID 18524775.
  7. ^ Gartler, G.; Kratky, C.; Gruber, K. (2007). "Structural determinants of the enantioselectivity of the hydroxynitrile lyase from Hevea brasiliensis". J. Biotechnol. 129 (1): 87–97. doi:10.1016/j.jbiotec.2006.12.009. PMID 17250917.
  8. ^ Wagner, U.G.; Schall, M.; Hasslacher, M.; Hayn, M.; Griengl, H.; Schwab, H.; Kratky, C. (1996). "Crystallization and preliminary X-ray diffraction studies of a hydroxynitrile lyase from Hevea brasiliensis". Acta Crystallogr. D. 52 (Pt 3): 591–593. doi:10.1107/s0907444995016830. PMID 15299689.
  9. ^ Schmidt, M.; Herve, S.; Klempier, N.; Griengl, H. (1996). "Preparation of optically active cyanohydrins using the (S)-hydroxynitrile lyase from Hevea brasiliensis". Tetrahedron. 52 (23): 7833–7840. doi:10.1016/0040-4020(96)00354-7.
  10. ^ Klempier, N.; Griengl, H. (1993). "Aliphatic (S)-cyanohydrins by enzyme catalyzed synthesis". Tetrahedron Lett. 34 (30): 4769–4772. doi:10.1016/s0040-4039(00)74084-6.
  11. ^ Poultan, J.E. (1990). "Cyanogenesis in Plants". Plant Physiol. 94 (2): 401–405. doi:10.1104/pp.94.2.401. PMC 1077245. PMID 16667728.
  12. ^ Ollis, D. L.; Cheah, E.; Cygler, M.; Dijkstra, B.; Frolow, F.; Franken, S. M.; Harel, M.; Remington, S. J.; Silman, I.; Schrag, J.; Sussman, J. L.; Verschueren, K. H. G. & Goldman, A. (1992). "The α/β hydrolase fold" (PDF). Protein Eng. 5 (3): 197–211. doi:10.1093/protein/5.3.197. hdl:11370/2d4c057d-1a67-437d-ad10-701f7a60f1e6. PMID 1409539.
  13. ^ Cui FC; Pan XL; Liu JY (2010). "Catalytic mechanism of hydroxynitrile lyase from Hevea brasiliensis: a theoretical investigation". J Phys Chem B. 114 (29): 9622–8. doi:10.1021/jp100373e. PMID 20593768.
  14. ^ Gruber K, Gartler G, Krammer B, Schwab H, Kratky C (2004). "Reaction mechanism of hydroxynitrile lyases of the α/β-hydrolase superfamily: the three-dimensional structure of the transient enzyme-substrate complex certifies the crucial role of LYS236". J Biol Chem. 279 (19): 20501–10. doi:10.1074/jbc.M401575200. PMID 14998991.
  15. ^ Padhi SK; Fujii R; Legatt GA; Fossum SL; Berchtold R; Kazlauskas RJ (2010). "Switching from an esterase to a hydroxynitrile lyase mechanism requires only two amino acid substitutions". Chem. Biol. 17 (8): 863–71. doi:10.1016/j.chembiol.2010.06.013. PMID 20797615.
  16. ^ Andexer JN, Staunig N, Eggert T, Kratky C, Pohl M, Gruber K (2002). "The active site of hydroxynitrile lyase from Prunus amygdalus: modeling studies provide new insights into the mechanism of cyanogenesis". Protein Sci. 11 (2): 292–300. doi:10.1110/PS.38102. PMC 2373431. PMID 11790839.
  17. ^ Dreveny I, Kratky C, Gruber K (2012). "Hydroxynitrile lyases with α/β-hydrolase fold: two enzymes with almost identical 3D structures but opposite enantioselectivities and different reaction mechanisms". ChemBioChem. 13 (13): 1932–9. doi:10.1002/cbic.201200239. PMC 3444685. PMID 22851196.
  18. ^ Sánchez-Perez, R.; Saez, F.; Borch, J.; Dicenta, F.; Moller, B. & Jorgensen, K. (2012). "Prunasin hydrolases during fruit development in sweet and bitter almonds". Plant Physiol. 158 (4): 1916–1932. doi:10.1104/pp.111.192021. PMC 3320195. PMID 22353576.
  19. ^ Purkarthofer, T.; Gruber, K.; Gruber-Khadjawi, M.; Waich, K.; Skranc, W.; Mink, D.; Griengl, H. (2006). "A Biocatalytic Henry Reaction—The Hydroxynitrile Lyase from Hevea brasiliensis Also Catalyzes Nitroaldol Reactions". Angewandte Chemie. 45 (21): 3454–3456. doi:10.1002/anie.200504230. PMID 16634109.

External links edit

December 15, 2023
hydroxynitrile, lyase, cyanohydrin, producing, hydroxynitrile, lyase, oxynitrilase, hbhnl, mehnl, hydroxynitrile, lyase, oxynitrilase, hbhnl, mehnl, selective, hydroxynitrile, lyase, cyanohydrin, carbonyl, lyase, cyanide, forming, hydroxynitrilase, enzyme, wit. S hydroxynitrile lyase EC 4 1 2 47 S cyanohydrin producing hydroxynitrile lyase S oxynitrilase S HbHNL S MeHNL hydroxynitrile lyase oxynitrilase HbHNL MeHNL S selective hydroxynitrile lyase S cyanohydrin carbonyl lyase cyanide forming hydroxynitrilase is an enzyme with systematic name S cyanohydrin lyase cyanide forming 1 2 3 4 5 6 7 8 9 10 This enzyme catalyses the interconversion between cyanohydrins and the carbonyl compounds derived from the cyanohydrin with free cyanide as in the following two chemical reactions an aliphatic S hydroxynitrile displaystyle rightleftharpoons an aliphatic aldehyde or ketone cyanide an aromatic S hydroxynitrile displaystyle rightleftharpoons an aromatic aldehyde cyanide S hydroxynitrile lyaseIdentifiersEC no 4 1 2 47DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumSearchPMCarticlesPubMedarticlesNCBIproteins In nature the liberation of cyanide serves as a defense mechanism against herbivores and microbial attack in plants 11 Hydroxynitrile lyases of the a b hydrolase fold are closely related to esterases All members of the a b hydrolase fold contain a conserved catalytic triad nucleophile histidine aspartate 12 The nucleophile in this case is a serine In contrast to esterases serine proteases lipases and other enzymes in this family the nucleophile in hydroxynitrile lyases functions as a proton acceptor 13 Key amino acid residues in this reaction are the lysine at position 236 and the threonine at position 11 14 Lys236 helps to orient the substrate while Thr11 serves to block the oxyanion hole that would convert the enzyme into an esterase 15 Commonly studied S selective hydroxynitrile lyases include MeHNL from Manihot esculenta and HbHNL from Hevea brasiliensis R selective hydroxynitrile lyases have also been found to exist in Arabidopsis thaliana AtHNL AtHNL is thought to catalyze this reaction by a different mechanism 16 Not all hydroxynitrile lyases belong to the a b hydrolase family PaHNL Prunus amygdalus R selective like AtHNL uses a flavin cofactor to catalyze cyanogenesis 17 Contents 1 Natural Substrates of Hydroxynitrile Lyases 2 Unnatural Substrates 3 References 4 External linksNatural Substrates of Hydroxynitrile Lyases editAcetone cyanohydrin has been determined to be the natural substrate of HbHNL though HbHNL also shows activity with mandelonitrile the natural substrate of PaHNL The cleavage of mandelonitrile into benzaldehyde and cyanide is what produces the characteristic amaretto smell of almonds 18 The natural substrate of AtHNL is unknown as no cyanohydrins have been detected in Arabidopis thaliana Unnatural Substrates editIn addition to cyanohydrin cleavage HNLs have been found to catalyze the nitroaldol reaction at low levels 19 References edit Forster S Roos J Effenberger F Wajant H Sprauer A 1996 The first recombinant hydroxynitrile lyase and its application in the synthesis of S cyanohydrins Angew Chem Int Ed 35 4 437 439 doi 10 1002 anie 199604371 Buhler H Effenberger F Forster S Roos J Wajant H 2003 Substrate specificity of mutants of the hydroxynitrile lyase from Manihot esculenta ChemBioChem 4 2 3 211 216 doi 10 1002 cbic 200390033 PMID 12616635 Semba H Dobashi Y Matsui T 2008 Expression of hydroxynitrile lyase from Manihot esculenta in yeast and its application in S mandelonitrile production using an immobilized enzyme reactor Biosci Biotechnol Biochem 72 6 1457 1463 doi 10 1271 bbb 70765 PMID 18540112 Avi M Wiedner R M Griengl H Schwab H 2008 Improvement of a stereoselective biocatalytic synthesis by substrate and enzyme engineering 2 hydroxy 4 oxocyclohexyl acetonitrile as the model Chemistry A European Journal 14 36 11415 11422 doi 10 1002 chem 200800609 PMID 19006143 von Langermann J Guterl J K Pohl M Wajant H Kragl U 2008 Hydroxynitrile lyase catalyzed cyanohydrin synthesis at high pH values Bioprocess Biosyst Eng 31 3 155 161 doi 10 1007 s00449 008 0198 4 PMID 18204865 Schmidt A Gruber K Kratky C Lamzin V S 2008 Atomic resolution crystal structures and quantum chemistry meet to reveal subtleties of hydroxynitrile lyase catalysis J Biol Chem 283 31 21827 21836 doi 10 1074 jbc m801056200 PMID 18524775 Gartler G Kratky C Gruber K 2007 Structural determinants of the enantioselectivity of the hydroxynitrile lyase from Hevea brasiliensis J Biotechnol 129 1 87 97 doi 10 1016 j jbiotec 2006 12 009 PMID 17250917 Wagner U G Schall M Hasslacher M Hayn M Griengl H Schwab H Kratky C 1996 Crystallization and preliminary X ray diffraction studies of a hydroxynitrile lyase from Hevea brasiliensis Acta Crystallogr D 52 Pt 3 591 593 doi 10 1107 s0907444995016830 PMID 15299689 Schmidt M Herve S Klempier N Griengl H 1996 Preparation of optically active cyanohydrins using the S hydroxynitrile lyase from Hevea brasiliensis Tetrahedron 52 23 7833 7840 doi 10 1016 0040 4020 96 00354 7 Klempier N Griengl H 1993 Aliphatic S cyanohydrins by enzyme catalyzed synthesis Tetrahedron Lett 34 30 4769 4772 doi 10 1016 s0040 4039 00 74084 6 Poultan J E 1990 Cyanogenesis in Plants Plant Physiol 94 2 401 405 doi 10 1104 pp 94 2 401 PMC 1077245 PMID 16667728 Ollis D L Cheah E Cygler M Dijkstra B Frolow F Franken S M Harel M Remington S J Silman I Schrag J Sussman J L Verschueren K H G amp Goldman A 1992 The a b hydrolase fold PDF Protein Eng 5 3 197 211 doi 10 1093 protein 5 3 197 hdl 11370 2d4c057d 1a67 437d ad10 701f7a60f1e6 PMID 1409539 Cui FC Pan XL Liu JY 2010 Catalytic mechanism of hydroxynitrile lyase from Hevea brasiliensis a theoretical investigation J Phys Chem B 114 29 9622 8 doi 10 1021 jp100373e PMID 20593768 Gruber K Gartler G Krammer B Schwab H Kratky C 2004 Reaction mechanism of hydroxynitrile lyases of the a b hydrolase superfamily the three dimensional structure of the transient enzyme substrate complex certifies the crucial role of LYS236 J Biol Chem 279 19 20501 10 doi 10 1074 jbc M401575200 PMID 14998991 Padhi SK Fujii R Legatt GA Fossum SL Berchtold R Kazlauskas RJ 2010 Switching from an esterase to a hydroxynitrile lyase mechanism requires only two amino acid substitutions Chem Biol 17 8 863 71 doi 10 1016 j chembiol 2010 06 013 PMID 20797615 Andexer JN Staunig N Eggert T Kratky C Pohl M Gruber K 2002 The active site of hydroxynitrile lyase from Prunus amygdalus modeling studies provide new insights into the mechanism of cyanogenesis Protein Sci 11 2 292 300 doi 10 1110 PS 38102 PMC 2373431 PMID 11790839 Dreveny I Kratky C Gruber K 2012 Hydroxynitrile lyases with a b hydrolase fold two enzymes with almost identical 3D structures but opposite enantioselectivities and different reaction mechanisms ChemBioChem 13 13 1932 9 doi 10 1002 cbic 201200239 PMC 3444685 PMID 22851196 Sanchez Perez R Saez F Borch J Dicenta F Moller B amp Jorgensen K 2012 Prunasin hydrolases during fruit development in sweet and bitter almonds Plant Physiol 158 4 1916 1932 doi 10 1104 pp 111 192021 PMC 3320195 PMID 22353576 Purkarthofer T Gruber K Gruber Khadjawi M Waich K Skranc W Mink D Griengl H 2006 A Biocatalytic Henry Reaction The Hydroxynitrile Lyase from Hevea brasiliensis Also Catalyzes Nitroaldol Reactions Angewandte Chemie 45 21 3454 3456 doi 10 1002 anie 200504230 PMID 16634109 External links edit S hydroxynitrile lyase at the U S National Library of Medicine Medical Subject Headings MeSH Portal nbsp Biology Retrieved from https en wikipedia org w index php title S hydroxynitrile lyase amp oldid 1187245276, wikipedia, wiki, book, books, library,

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