Skip to main content
Log in

Hydrophobic Formic Acid Esters for Cofactor Regeneration in Aqueous/Organic Two-Liquid Phase Systems

  • Original Paper
  • Published:
Topics in Catalysis Aims and scope Submit manuscript

Abstract

Hydrophobic formic acid esters have been established as alternative cosubstrates for the formate dehydrogenase (FDH)-catalyzed regeneration of reduced nicotinamides. With this approach challenges related to the ionic nature of the commonly used formate salts, particularly their exclusive water-solubility, can be overcome. Octyl formate was demonstrated to serve as organic phase solubilizing hydrophobic reagents as well as serving as a source of reducing equivalents to enable FDH-catalyzed regeneration of NADH. This system was used to drive a monooxygenase-catalyzed hydroxylation reaction. Phase transfer limitations appear to be the overall rate-limitation of the biphasic reaction system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Weckbecker A, Groger H, Hummel W (2010) Regeneration of nicotinamide coenzymes: principles and applications for the synthesis of chiral compounds. In: Wittmann C, Krull WR (eds) Biosystems engineering I: creating superior biocatalysts, vol 120. Advances in biochemical engineering-biotechnology. Springer, Berlin, pp 195–242. doi:10.1007/10_2009_55

    Chapter  Google Scholar 

  2. van der Donk WA, Zhao H (2003) Recent developments in pyridine nucleotide regeneration. Curr Opin Biotechnol 14(4):421–426

    Article  Google Scholar 

  3. Hollmann F, Arends IWCE, Holtmann D (2011) Enzymatic reductions for the chemist. Green Chem 13(9):2285–2313

    Article  CAS  Google Scholar 

  4. Hollmann F, Arends IWCE, Buehler K, Schallmey A, Buhler B (2011) Enzyme-mediated oxidations for the chemist. Green Chem 13:226–265

    Article  CAS  Google Scholar 

  5. Hollmann F, Arends Isabel WCE, Buehler K (2010) Biocatalytic redox reactions for organic synthesis: nonconventional regeneration methods. ChemCatChem 2(7):762–782

    Article  CAS  Google Scholar 

  6. Rodriguez C, Lavandera I, Gotor V (2012) Recent advances in cofactor regeneration systems applied to biocatalyzed oxidative processes. Curr Org Chem 16(21):2525–2541. doi:10.2174/138527212804004643

    Article  CAS  Google Scholar 

  7. Shaked Z, Whitesides GM (1980) Enzyme-catalyzed organic synthesis—NADH regeneration by using formate dehydrogenase. J Am Chem Soc 102(23):7104–7105. doi:10.1021/ja00543a038

    Article  CAS  Google Scholar 

  8. Sonoike S, Itakura T, Kitamura M, Aoki S (2012) One-pot chemoenzymatic synthesis of chiral 1,3-diols using an enantioselective aldol reaction with chiral Zn2+ complex catalysts and enzymatic reduction using oxidoreductases with cofactor regeneration. Chem-Asian J 7(1):64–74. doi:10.1002/asia.201100584

    Article  CAS  Google Scholar 

  9. Chen Y, Goldberg SL, Hanson RL, Parker WL, Gill I, Tully TP, Montana MA, Goswami A, Patel RN (2011) Enzymatic preparation of an (S)-amino acid from a racemic amino acid. Org Proc Res Dev 15(1):241–248. doi:10.1021/op1001534

    Article  Google Scholar 

  10. Kuehnel K, Maurer SC, Galeyeva Y, Frey W, Laschat S, Urlacher VB (2007) Hydroxylation of dodecanoic acid and (2R,4R,6R,8R)-tetramethyldecanol on a preparative scale using an NADH-dependent CYP102A1 mutant. Adv Synth Catal 349(8–9):1451–1461. doi:10.1002/adsc.200700054

    Article  CAS  Google Scholar 

  11. Maurer SC, Schulze H, Schmid RD, Urlacher VB (2003) Immobilisation of P450 BM-3 and an NADP+ cofactor recycling system: towards a technical application of heme-containing monooxygenases in fine chemical synthesis. Adv Synth Catal 345(6–7):802–810

    Article  CAS  Google Scholar 

  12. Hofstetter K, Lutz J, Lang I, Witholt B, Schmid A (2004) Coupling of biocatalytic asymmetric epoxidation with nadh regeneration in organic-aqueous emulsions. Angew Chem Int Ed 43(16):2163–2166

    Article  CAS  Google Scholar 

  13. Lutz J, Mozhaev VV, Khmelnitsky YL, Witholt B, Schmid A (2002) Preparative application of 2-hydroxybiphenyl 3-monooxygenase with enzymatic cofactor regeneration in organic-aqueous reaction media. J Mol Catal B Enzym 19–20:177–187

    Article  Google Scholar 

  14. Schmid A, Vereyken I, Held M, Witholt B (2001) Preparative regio- and chemoselective functionalization of hydrocarbons catalyzed by cell free preparations of 2-hydroxybiphenyl 3-monooxygenase. J Mol Catal B Enzym 11(4–6):455–462

    Article  CAS  Google Scholar 

  15. Eckstein M, Villela M, Liese A, Kragl U (2004) Use of an ionic liquid in a two-phase system to improve an alcohol dehydrogenase catalysed reduction. Chem Commun 9:1084–1085. doi:10.1039/b401065e

    Article  Google Scholar 

  16. Jakoblinnert A, Mladenov R, Paul A, Sibilla F, Schwaneberg U, Ansorge-Schumacher MB, de Maria PD (2011) Asymmetric reduction of ketones with recombinant E. coli whole cells in neat substrates. Chem Commun 47(44):12230–12232

    Article  CAS  Google Scholar 

  17. Churakova E, Arends IWCE, Hollmann F (2013) Increasing the productivity of peroxidase-catalyzed oxyfunctionalization: a case study on the potential of two-liquid-phase systems. ChemCatChem 5:565–568. doi:10.1002/cctc.201200490

    Article  CAS  Google Scholar 

  18. Frohlich P, Albert K, Bertau M (2011) Formate dehydrogenase—a biocatalyst with novel applications in organic chemistry. Org Biomol Chem 9(22):7941–7950

    Article  Google Scholar 

  19. Hollmann F, Schmid A, Steckhan E (2001) The first synthetic application of a monooxygenase employing indirect electrochemical NADH regeneration. Angew Chem Int Ed 40(1):169–171

    Article  CAS  Google Scholar 

  20. Held M, Schmid A, Kohler HPE, Suske W, Witholt B, Wubbolts MG (1999) An integrated process for the production of toxic catechols from toxic phenols based on a designer biocatalyst. Biotechnol Bioeng 62(6):641–648

    Article  CAS  Google Scholar 

  21. Held M, Suske W, Schmid A, Engesser KH, Kohler HPE, Witholt B, Wubbolts MG (1998) Preparative scale production of 3-substituted catechols using a novel monooxygenase from Pseudomonas azelaica HBP 1. J Mol Catal B Enzym 5(1–4):87–93

    Article  CAS  Google Scholar 

  22. Suske WA, Held M, Schmid A, Fleischmann T, Wubbolts MG, Kohler H-PE (1997) Purification and characterization of 2-hydroxybiphenyl 3-monooxygenase, a novel NADH-dependent, FAD-containing aromatic hydroxylase from Pseudomonas azelaica HBP1. J Biol Chem 272(39):24257–24265. doi:10.1074/jbc.272.39.24257

    Article  CAS  Google Scholar 

  23. Schmid A, Kohler HPE, Engesser KH (1998) E-coli JM109 pHBP461, a recombinant biocatalyst for the regioselective monohydroxylation of ortho-substituted phenols to their corresponding 3-substituted catechols. J Mol Catal B Enzym 5(1–4):311–316

    Article  CAS  Google Scholar 

  24. Slusarczyk H, Felber S, Kula MR, Pohl M (2000) Stabilization of NAD-dependent formate dehydrogenase from Candida boidinii by site-directed mutagenesis of cysteine residues. Eur J Biochem 267(5):1280–1289. doi:10.1046/j.1432-1327.2000.01123.x

    Article  CAS  Google Scholar 

  25. Suske WA, van Berkel WJH, Kohler H-PE (1999) Catalytic mechanism of 2-hydroxybiphenyl 3-monooxygenase, a flavoprotein from Pseudomonas azelaica HBP1. J Biol Chem 274(47):33355–33365. doi:10.1074/jbc.274.47.33355

    Article  CAS  Google Scholar 

  26. Bornscheuer U, Kazlauskas R (2006) Hydrolases in organic synthesis, 2nd edn. Wiley, Weinheim

    Google Scholar 

  27. Musa MM, Phillips RS (2011) Recent advances in alcohol dehydrogenase-catalyzed asymmetric production of hydrophobic alcohols. Catal Sci Technol 1(8):1311–1323. doi:10.1039/c1cy00160d

    Article  CAS  Google Scholar 

  28. Thorey P, Knez Z, Habulin M (2010) Alcohol dehydrogenase in non-aqueous media using high-pressure technologies: reaction set-up and deactivation determination. J Chem Technol Biotechnol 85(7):1011–1016. doi:10.1002/jctb.2411

    Article  CAS  Google Scholar 

  29. Lavandera I, Kern A, Schaffenberger M, Gross J, Glieder A, de Wildeman S, Kroutil W (2008) An exceptionally DMSO-tolerant alcohol dehydrogenase for the stereoselective reduction of ketones. ChemSusChem 1(5):431–436. doi:10.1002/cssc.200800032

    Article  CAS  Google Scholar 

  30. Orlich B, Berger H, Lade M, Schomacker R (2000) Stability and activity of alcohol dehydrogenases in W/O-microemulsions: enantioselective reduction including cofactor regeneration. Biotechnol Bioeng 70(6):638–646

    Article  CAS  Google Scholar 

  31. Matsuda T, Harada T, Nakamura K (2000) Alcohol dehydrogenase is active in supercritical carbon dioxide. Chem Comm 23(15):1367–1368

    Article  Google Scholar 

  32. Grunwald J, Wirz B, Scollar MP, Klibanov AM (1986) Asymmetric oxidoreductions catalyzed by alcohol dehydrogenase in organic solvents. J Am Chem Soc 108(21):6732–6734. doi:10.1021/ja00281a044

    Article  CAS  Google Scholar 

  33. Klibanov AM (2003) Asymmetric enzymatic oxidoreductions in organic solvents. Curr Opin Biotechnol 14(4):427–431

    Article  CAS  Google Scholar 

  34. Klibanov AM (2001) Improving enzymes by using them in organic solvents. Nature 409(6817):241–246

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This Project was supported by the BIOTRAINS Marie Curie Initial Training Network, financed by the European Union through the 7th Framework People Programme (Grant agreement number 238531).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank Hollmann.

Additional information

Ekaterina Churakova and Bartłomiej Tomaszewski contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Churakova, E., Tomaszewski, B., Buehler, K. et al. Hydrophobic Formic Acid Esters for Cofactor Regeneration in Aqueous/Organic Two-Liquid Phase Systems. Top Catal 57, 385–391 (2014). https://doi.org/10.1007/s11244-013-0195-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11244-013-0195-y

Keywords

Navigation