(S)-hydroxynitrile lyase

(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 number4.1.2.47
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

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

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

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

gollark: Impossible. I have not yet investigated.
gollark: ++remind 10m relink apionet also
gollark: ++remind 10m investigate
gollark: I'll investigate.
gollark: Imagemagick can probably be convinced to handle the transparency right.

References
  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. 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. 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.
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