Catalysis Letters

, Volume 148, Issue 12, pp 3678–3684 | Cite as

One-Pot Preparation of d-Amino Acids Through Biocatalytic Deracemization Using Alanine Dehydrogenase and ω-Transaminase

  • Sang-Woo Han
  • Jong-Shik ShinEmail author


d-Amino acids are pharmaceutically important building blocks, leading to a great deal of research efforts to develop cost-effective synthetic methods. Preparation of d-amino acids by deracemization has been conceptually attractive owing to facile synthesis of racemic amino acids by Strecker synthesis. Here, we demonstrated biocatalytic deracemization of aliphatic amino acids into d-enantiomers by running cascade reactions; (1) stereoinversion of l-amino acid to a d-form by amino acid dehydrogenase and ω-transaminase and (2) regeneration of NAD+ by NADH oxidase. Under the cascade reaction conditions containing 100 mM isopropylamine and 1 mM NAD+, complete deracemization of 100 mM dl-alanine was achieved after 24 h with 95% reaction yield of d-alanine (> 99% eeD, 52% isolation yield).

Graphical Abstract


Cascade reaction Deracemization d-Amino acids Alanine dehydrogenase ω-Transaminase 



This work was funded by the National Research Foundation of Korea under the Basic Science Research Program (2016R1A2B400840). We thank Mrs Sae-Rom Park for technical assistance in the cloning of NOX.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest to disclose.

Supplementary material

10562_2018_2565_MOESM1_ESM.docx (969 kb)
Supplementary material 1 (DOCX 968 KB)


  1. 1.
    Fuchs SA, Berger R, Klomp LW, de Koning TJ (2005) Mol Genet Metab 85:168–180CrossRefGoogle Scholar
  2. 2.
    Kiriyama Y, Nochi H (2016) Scientifica (Cairo) 2016:6494621Google Scholar
  3. 3.
    Genchi G (2017) Amino Acids 49:1521–1533CrossRefGoogle Scholar
  4. 4.
    Gao X, Ma Q, Zhu H (2015) Appl Microbiol Biotechnol 99:3341–3349CrossRefGoogle Scholar
  5. 5.
    Martinez-Rodriguez S, Martinez-Gomez AI, Rodriguez-Vico F, Clemente-Jimenez JM, Heras-Vazquez LFJ (2010) Chem Biodiv 7:1531–1548CrossRefGoogle Scholar
  6. 6.
    Tsai G, Coyle J (2001) US Patent 6,228,875 B1Google Scholar
  7. 7.
    Huirne JA, Lambalk CB (2001) Lancet 358:1793–1803CrossRefGoogle Scholar
  8. 8.
    Yuasa Y, Nagakura A, Tsuruta H (2001) J Agric Food Chem 49:5013–5018CrossRefGoogle Scholar
  9. 9.
    Ma JA (2003) Angew Chem Int Ed 42:4290–4299CrossRefGoogle Scholar
  10. 10.
    Breuer M, Ditrich K, Habicher T, Hauer B, Kesseler M, Sturmer R, Zelinski T (2004) Angew Chem Int Ed 43:788–824CrossRefGoogle Scholar
  11. 11.
    Xue Y-P, Cao C-H, Zheng Y-G (2018) Chem Soc Rev 47:1516–1561CrossRefGoogle Scholar
  12. 12.
    Vedha-Peters K, Gunawardana M, Rozzell JD, Novick SJ (2006) J Am Chem Soc 128:10923–10929CrossRefGoogle Scholar
  13. 13.
    Ager DJ, Fotheringham IG (2001) Curr Opin Drug Discov Dev 4:800–807Google Scholar
  14. 14.
    Park ES, Dong JY, Shin JS (2013) Org Biomol Chem 11:6929–6933CrossRefGoogle Scholar
  15. 15.
    Park ES, Dong JY, Shin JS (2013) ChemCatChem 5:3538–3542CrossRefGoogle Scholar
  16. 16.
    Park ES, Dong JY, Shin JS (2014) Appl Microbiol Biotechnol 98:651–660CrossRefGoogle Scholar
  17. 17.
    Merino P, Marqués-López E, Tejero T, Herrera RP (2009) Tetrahedron 65:1219–1234CrossRefGoogle Scholar
  18. 18.
    Yano S, Haruta H, Ikeda T, Kikuchi T, Murakami M, Moriguchi M, Wakayama M (2011) J Chromatogr B 879:3247–3252CrossRefGoogle Scholar
  19. 19.
    Carboni C, Gardossi L, Tamiola K, Janssen DB, Quaedflieg PJLM (2006) Tetrahedron Asymmetry 17:245–251CrossRefGoogle Scholar
  20. 20.
    Krieg L, Ansorge-Schumacher MB, Kula MR (2002) Adv Synth Catal 344:965–973CrossRefGoogle Scholar
  21. 21.
    Isobe K, Tamauchi H, Fuhshuku K, Nagasawa S, Asano Y (2010) Enzyme Res 2010:567210CrossRefGoogle Scholar
  22. 22.
    Wegman MA, Janssen MHA, van Rantwijk F, Sheldon RA (2001) Adv Synth Catal 343:559–576CrossRefGoogle Scholar
  23. 23.
    Servi S, Tessaro D, Pedrocchi-Fantoni G (2008) Coord Chem Rev 252:715–726CrossRefGoogle Scholar
  24. 24.
    Park ES, Shin JS (2014) Adv Synth Catal 356:3505–3509CrossRefGoogle Scholar
  25. 25.
    Schatzle S, Höhne M, Redestad E, Robins K, Bornscheuer UT (2009) Anal Chem 81:8244–8248CrossRefGoogle Scholar
  26. 26.
    Bhushan R, Bruckner H (2004) Amino Acids 27:231–247CrossRefGoogle Scholar
  27. 27.
    Malik MS, Park ES, Shin JS (2012) Appl Microbiol Biotechnol 94:1163–1171CrossRefGoogle Scholar
  28. 28.
    Seo YM, Mathew S, Bea HS, Khang YH, Lee SH, Kim BG, Yun H (2012) Org Biomol Chem 10:2482–2485CrossRefGoogle Scholar
  29. 29.
    Geueke B, Riebel B, Hummel W (2003) Enzyme Microb Technol 32:205–211CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiotechnologyYonsei UniversitySeoulSouth Korea

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