Applied Microbiology and Biotechnology

, Volume 76, Issue 5, pp 1001–1008 | Cite as

Biocatalytic racemization of sec-alcohols and α-hydroxyketones using lyophilized microbial cells

  • Bettina M. Nestl
  • Constance V. Voss
  • Anne Bodlenner
  • Ursula Ellmer-Schaumberger
  • Wolfgang Kroutil
  • Kurt Faber
Biotechnological Products and Process Engineering

Abstract

Biocatalytic racemization of aliphatic and aryl-aliphatic sec-alcohols and α-hydroxyketones (acyloins) was accomplished using whole resting cells of bacteria, fungi, and one yeast. The mild (physiological) reaction conditions ensured the suppression of undesired side reactions, such as elimination or condensation. Cofactor and inhibitor studies suggest that the racemization proceeds through an equilibrium-controlled enzymatic oxidation–reduction sequence via the corresponding ketones or α-diketones, respectively, which were detected in various amounts. Ketone formation could be completely suppressed by exclusion of molecular oxygen.

Figure

Biocatalytic racemization whole microbial cells

Keywords

sec-alcohols Acyloins Isomerization Biotransformation Racemization 

Supplementary material

References

  1. Berkessel A, Sebastian-Ibarz ML, Mueller T (2006) Lipase/aluminum-catalyzed dynamic kinetic resolution of secondary alcohols. Angew Chem Int Ed Engl 45:6567–6570CrossRefGoogle Scholar
  2. Boren L, Martin-Matute B, Xu Y, Cordova A, Baeckvall JE (2006) (S)-Selective kinetic resolution and chemoenzymatic dynamic kinetic resolution of secondary alcohols. Chem Eur J 12:225–232CrossRefGoogle Scholar
  3. Cheng Y, Zhang F, Rano TA, Lu Z, Scheleif WA, Gabryelski L, Olsen DB, Stahlhunt M, Rutkowski CA, Lin JH, Jin L, Emini EA, Chapman KT, Tata JR (2002) Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-Resistant viral strains. Bioorg Med Chem Lett 12:2419–2422CrossRefGoogle Scholar
  4. Demir AS, Hamamci H, Sesenoglu O, Aydogan F, Capanoglu D, Neslihanoglu R (2001) Simple chemoenzymatic access to enantiopure pharmacologically interesting (R)-2-hydroxypropiophenones. Tetrahedron Asymmetry 12:1953–1956CrossRefGoogle Scholar
  5. Ebbers EJ, Ariaans GJA, Houbiers JPM, Bruggink A, Zwanenburg B (1997) Controlled racemization of optically active organic compounds: prospects for asymmetric transformation. Tetrahedron 53:9417–9476CrossRefGoogle Scholar
  6. Engel S, Vyazmensky M, Geresh S, Barak Z, Chipman DM (2003) Acetohydroxyacid synthase: a new enzyme for chiral synthesis of R-phenylacetylcarbinol. Biotechnol Bioeng 83:640–833CrossRefGoogle Scholar
  7. Faber K (2001) Non-sequential processes for the transformation of a racemate into a single stereoisomeric product: proposal for stereochemical classification. Chem Eur J 7:504–510CrossRefGoogle Scholar
  8. Felfer U, Goriup M, Koegl MF, Wagner U, Larissegger-Schnell B, Faber K, Kroutil W (2005) The substrate spectrum of mandelate racemase: minimum structural requirements for substrates and substrate model. Adv Synth Catal 347: 951–956CrossRefGoogle Scholar
  9. Giovannini PP, Medici A, Bergamini CM, Rippa M (1996) Properties of diacetyl (acetoin) reductase from Bacillus stearothermophilus. Bioorg Med Chem 4:1197–1201CrossRefGoogle Scholar
  10. Glueck SM, Larissegger-Schnell B, Csar K, Kroutil W, Faber K (2005a) Biocatalytic racemisation of α-hydroxycarboxylic acids at physiological conditions. Chem Commun 14:1904–1905CrossRefGoogle Scholar
  11. Glueck SM, Pirker M, Nestl BM, Ueberbacher BT, Larissegger-Schnell B, Csar K, Hauer B, Stuermer R, Kroutil W, Faber K (2005b) Biocatalytic racemization of aliphatic, arylaliphatic, and aromatic α-hydroxycarboxylic acids. J Org Chem 70:4028–4032CrossRefGoogle Scholar
  12. Goswami A, Mirfakhrae KD, Patel RN (1999) Deracemization of racemic 1,2-diol by biocatalytic stereoinversion. Tetrahedron Asymmetry 10:4239–4244CrossRefGoogle Scholar
  13. Gruber CC, Lavandera I, Faber K, Kroutil W (2006) From a racemate to a single enantiomer: deracemization by stereoinversion. Adv Synth Catal 348:1789–1805CrossRefGoogle Scholar
  14. Hata H, Shimizu S, Hattori S, Yamada H (1990) Stereoselective reduction of diketones by a novel carbonyl reductase from Candida parapsilosis. J Org Chem 55:4377–4380CrossRefGoogle Scholar
  15. Heidlas J, Tressl R (1990) Purification and properties of two oxidoreductases catalyzing the enantioselective reduction of diacetyl and other diketones from baker’s yeast. Eur J Biochem 188:165–174CrossRefGoogle Scholar
  16. Hirscher T, Gocke D, Fernandez M, Hoyos P, Alcantara AR, Sinisterra JV, Hartmeier W, Ansorge-Schumacher MB (2005) Stereoselective synthesis of novel benzoins catalysed by benzaldehyde lyase in a gel-stabilised two-phase system. Tetrahedron 61:7378–7383CrossRefGoogle Scholar
  17. Hoyos P, Fernandez M, Sinisterra JV, Alcantara AR (2006) Dynamic kinetic resolution of benzoins by lipase-metal combo catalysis. J Org Chem 71:7632–7637CrossRefGoogle Scholar
  18. Hummel W, Kula MR (1989) Dehydrogenases for the synthesis of chiral compounds. Eur J Biochem 184:1–13CrossRefGoogle Scholar
  19. Hummel W, Schuette H, Kula MR (1985) D-2-hydroxyisocaproate dehydrogenase from Lactobacillus casei. Appl Microbiol Biotechnol 21:7–15CrossRefGoogle Scholar
  20. Inoue K, Makino Y, Itoh N (2005) Production of (R)-chiral alcohols by a hydrogen-transfer bioreduction with NADH-dependent Leifsonia alcohol dehydrogenase (LSADH). Tetrahedron Asymmetry 16:2539–2549CrossRefGoogle Scholar
  21. Jiang R, Bommarius AS (2004) An enzymatic process to α-ketoglutarate from l-glutamate: the coupled system l-glutamate dehydrogenase/NADH oxidase. Tetrahedron Asymmetry 15:2939–2944CrossRefGoogle Scholar
  22. Jiang R, Riebel BR, Bommarius AS (2005) Comparison of alkyl hydroperoxide reductase (AhpR) and water-forming NADH oxidase from Lactococcus lactis ATCC 19435. Adv Synth Catal 347:1139–1146CrossRefGoogle Scholar
  23. Kallwass HKW (1992) Potential of R-2-Hydroxyisocaproate dehydrogenase from Lactobacillus casei for stereospecific reductions. Enzyme Microb Technol 14:28–35CrossRefGoogle Scholar
  24. Kaluzna IA, Feske BD, Wittayanan W, Ghiviringa I, Stewart JD (2005a) Stereoselective, biocatalytic reductions of α-chloro-β−keto esters. J Org Chem 70:342–345CrossRefGoogle Scholar
  25. Kaluzna IA, Rozzell JD, Kambourakis S (2005b) Ketoreductases: stereoselective catalysts for the facile synthesis of chiral alcohols. Tetrahedron Asymmetry 16:3682–3689CrossRefGoogle Scholar
  26. Kim N, Ko SB, Kwon MS, Kim MJ, Park J (2005) Air-stable racemization catalyst for dynamic kinetic resolution of secondary alcohols at room temperature. Org Lett 7:4523–4526CrossRefGoogle Scholar
  27. Kroutil W, Mang H, Edegger K, Faber K (2004) Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols. Curr Opin Chem Biol 8:120–126CrossRefGoogle Scholar
  28. Larissegger-Schnell B, Faber K, Kroutil W (2003) Enzymatic racemisation and its application to synthetic biotransformations. Adv Synth Catal 345:653–666CrossRefGoogle Scholar
  29. Lunardi I, Conceicao GJA, Moran PJS, Rodrigues JAR (2005) Highly stereoselective preparation of (3R,4S)-3,4-chromanediol by deracemization of (±)-3-hydroxy-4-chromanone by Trichosporon cutaneum. Tetrahedron Asymmetry 16:2515–2519CrossRefGoogle Scholar
  30. Mueller M, Wolberg M, Schubert T, Hummel W (2005) Enzyme-catalyzed regio- and enantioselective ketone reductions. In: Advances in Biochemical Engineering/Biotechnology (eds) Technology transfer in biotechnology: from lab to industry to production. Springer, Berlin Heidelberg New York, pp 261–287Google Scholar
  31. Nakamura K, Yamanaka R, Matsuda T, Harada T (2003) Recent developments in asymmetric reduction of ketones by biocatalysts. Tetrahedron Asymmetry 14:2659–2681CrossRefGoogle Scholar
  32. Nestl BM, Kroutil W, Faber K (2006a) Biocatalytic racemization of α-hydroxy ketones (Acyloins) at physiological conditions using Lactobacillus paracasei DSM 20207. Adv Synth Catal 348:873–876CrossRefGoogle Scholar
  33. Nestl BM, Glueck SM, Hall M, Kroutil W, Stuermer R, Hauer B, Faber K (2006b) Biocatalytic racemization of (Hetero)aryl-aliphatic α-hydroxycarboxylic acids by Lactobacillus spp. Proceeds via an oxidation-reduction sequence. Eur J Org Chem 2006:4573–4577CrossRefGoogle Scholar
  34. Oedman P, Wessjohann LA, Bornscheuer UT (2005) Chemoenzymatic dynamic kinetic resolution of acyloins. J Org Chem 70:9551–9555CrossRefGoogle Scholar
  35. Pamies O, Baeckvall JE (2003) Combination of enzymes and metal catalysts. A powerful approach in asymmetric catalysis. Chem Rev 103:3247–3261CrossRefGoogle Scholar
  36. Patel RN (2001) Biocatalytic synthesis of intermediates for the synthesis of chiral drug substances. Curr Opin Biotechnol 12:587–604CrossRefGoogle Scholar
  37. Riebel BR, Gibbs PR, Wellborn WB, Bommarius AS (2002) Cofactor regeneration of NAD+ from NADH: novel water-forming NADH oxidases. Adv Synth Catal 344:1156–1168CrossRefGoogle Scholar
  38. Riebel BR, Gibbs PR, Wellborn WB, Bommarius AS (2003) Cofactor regeneration of both NAD+ from NADH and NADP+ from NADPH:NADH oxidase from Lactobacillus sanfranciscensis. Adv Synth Catal 345:707–712CrossRefGoogle Scholar
  39. Riermeier TH, Gross P, Monsees A, Hoff M, Trauthwein H (2005) Dynamic kinetic resolution of secondary alcohols with a readily available ruthenium-based racemization catalyst. Tetrahedron Lett 46:3404–3406CrossRefGoogle Scholar
  40. Rosche B, Breuer M, Hauer B, Rogers PL (2004) Biphasic aqueous/organic biotransformation of acetaldehyde and benzaldehyde by Zymomonas mobilis pyruvate decarboxylase. Biotechnol Bioeng 86:788–794CrossRefGoogle Scholar
  41. Saratani Y, Uheda E, Yamamoto H, Nishimura A, Yoshizako F (2003) Purification and properties of a carbonyl reductase involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate from Cylindrocarpon sclerotigenum IFO 31855. Biosci Biotechnol Biochem 67:1417–1420CrossRefGoogle Scholar
  42. Sarrazin E, Dubourdieu D, Darriet P (2007) Characterization of key-aroma compounds of botrytized wines, influence of grape botrytization. Food Chem 103:536–545CrossRefGoogle Scholar
  43. Scheid G, Kuit W, Ruijter E, Orru RVA, Henke E, Bornscheuer U, Wessjohann LA (2004) A new route to protected acyloins and their enzymatic resolution with lipases. Eur J Org Chem 2004:1063–1074CrossRefGoogle Scholar
  44. Schuette H, Hummel W, Kula MR (1984) L-2-hydroxyisocaproate dehydrogenase-a new enzyme from Lactobacillus confusus for the stereospecific reduction of 2-ketocarboxylic acids. Appl Microbiol Biotechnol 19:167–176CrossRefGoogle Scholar
  45. Shibata K, Shirassuna K, Motegi K, Hera Y, Abe H, Yamada R (2000) Purification and properties of alanine racemase from crayfish Procambarus clarkii. Comp Biochem Physiol B 126:599–608CrossRefGoogle Scholar
  46. Simon H, Bader J, Guenther H, Neumann S, Thanos J (1985) Chiral compounds synthesized by biocatalytic reductions [New Synthetic Methods (51)]. Angew Chem Int Ed Engl 24:539–553CrossRefGoogle Scholar
  47. Smallridge AJ, Trewhalla MA, Maurice A, Wilkinson AK (2003) Methods for the synthesis of amines such as ephedrine and intermediates via reductive animation of ketones. Patent WO 2003018531 A1 20030306Google Scholar
  48. Spies MA, Woodward JJ, Watnik MR, Toney MD (2004) Alanine racemase free energy profiles from global analyses of progress curves. J Am Chem Soc 126:7464–7475CrossRefGoogle Scholar
  49. Stampfer W, Kosjek B, Moitzi C, Kroutil W, Faber K (2002) Biocatalytic asymmetric hydrogen transfer. Angew Chem Int Ed Engl 41:1014–1017CrossRefGoogle Scholar
  50. Tanner ME (2002) Understanding nature’s strategies for enzyme-catalyzed racemization and epimerization. Acc Chem Res 35:237–246CrossRefGoogle Scholar
  51. Turner NJ (2004) Enzyme catalysed deracemization and dynamic kinetic resolution reactions. Curr Opin Chem Biol 8:114–119CrossRefGoogle Scholar
  52. van Nispen SFGM, van Buijtenen J, Vekemans JAJM, Meuldijk J, Hulshof LA (2006) Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex. Tetrahedron Asymmetry 17:2299–2305CrossRefGoogle Scholar
  53. Wolken WAM, ten Have R, van der Werf MJ (2000) Amino acid-catalyzed conversion of citral: cis-trans isomerization and its conversion into 6-methyl-5-hepten-2-one and acetaldehyde. J Agric Food Chem 48:4305–5401CrossRefGoogle Scholar
  54. Wuyts S, Temmerman K De, Vos DE De, Jacobs PA (2005) Acid zeolites as alcohol racemization catalysts: screening and application in biphasic dynamic kinetic resolution. Chem Eur J 11:386–397CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Bettina M. Nestl
    • 1
    • 2
  • Constance V. Voss
    • 1
  • Anne Bodlenner
    • 1
    • 2
  • Ursula Ellmer-Schaumberger
    • 1
    • 2
  • Wolfgang Kroutil
    • 1
  • Kurt Faber
    • 1
  1. 1.Department of Chemistry, Organic and Bioorganic ChemistryUniversity of GrazGrazAustria
  2. 2.Research Centre Applied BiochemistryGrazAustria

Personalised recommendations