Skip to main content
Log in

Enzymatic synthesis of β-lactam acids (review)

  • Published:
Applied Biochemistry and Microbiology Aims and scope Submit manuscript

Abstract

The currently known methods of enzymatic β-lactam synthesis, as well as the enzymes and heterogeneous biocatalysts used for this purpose, are presented, and the published reports on advances in the field of enzymatic synthesis of selected antibiotics belonging to the groups of penicillin acids and cephalosporin acids are summarized in the present review. The key conditions and parameters of biocatalytic processes, such as the biocatalyst form, concentration of the precursor compounds, solvent type, pH, temperature, etc. are analyzed and compared, and guidelines for further optimization of β-lactam synthesis are given. The present review may be of use for a wide range of readers, as well as to enzymology and biotechnology experts.

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.

Similar content being viewed by others

References

  1. Van Krimpen, P.C., Van Bennekom, W.P., and Bult, A., Pharm. Weekbl. Sci., 1987, vol. 9, no. 1, pp. 1–23.

    PubMed  Google Scholar 

  2. Elks, J., Drugs, 1987, vol. 34, suppl. 2, pp. 240–246.

    Article  PubMed  Google Scholar 

  3. Nys, P.S., Kurochkina, V.B., Sklyarenko, A.V., and Egorov, M.A., Antibiot. Khimioter., 2000, vol. 45, no. 11, pp. 36–42.

    CAS  PubMed  Google Scholar 

  4. Kurochkina, V.B. and Nys, P.S., Antibiot. Khimioter., 2002, vol. 47, no. 2, pp. 29–37.

    CAS  PubMed  Google Scholar 

  5. Kurochkina, V.B. and Nys, P.S., Khim-Farm. Zh., 2003, vol. 37, no. 126, pp. 33–40.

    Google Scholar 

  6. Kurochkina, V.B., Sklyarenko, AV., Satarova, J.E., and Yarotsky, S.V., Bioprocess Biosyst. Eng., 2011, vol. 34, no. 9, pp. 1103–1117.

    Article  CAS  PubMed  Google Scholar 

  7. Elander, R.P., Appl. Microbiol. Biotechnol., 2003, vol. 61, nos 5–6, pp. 385–392.

    Article  CAS  PubMed  Google Scholar 

  8. Schmidt, F-R., in The Mycota. X Industrial Applications, 2nd. ed., Esser, K. and Hofrichter, M., Eds., Berlin, Heidelberg: Springer-Verlag, vol. 5, pp. 101–121.

  9. Volpato, G., Rodrigues, R.C., and Fernandez-Lafuente, R., Curr. Med. Chem., 2010, vol. 17, no. 32, pp. 3855–3873.

    Article  CAS  PubMed  Google Scholar 

  10. Kurochkina, V.B. and Sklyarenko, A.V., Antibiot. Khimioter., 2005, vol. 50, no. 5–6, pp. 39–58.

    CAS  PubMed  Google Scholar 

  11. Sklyarenko, A.V., Kurochkina, V.B., and Egorov, A.M., in New Research on Biotechnology in Biology and Medicine, Egorov, A.M. and Zaikov, G., Eds., Nova Science Publishers, 2006, ch. 8, pp. 73–86.

  12. Synthesis of beta-Lactam Antibiotics: Chemistry, Biocatalysis and Process Integration, Bruggink, A., Ed., Dordrecht: Kluver Academic Publishers, 2001.

  13. Deaguero, A.L., Blum, J.K., and Bommarius, A.S., in Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, Flickinger, M.C., Ed., John Wiley and Sons, 2010, pp. 535–567.

  14. Barber, M.S., Giesecke, U., Reichert, A., and Minas, W., Adv. Biochem. Eng. Biotechnol., 2004, vol. 88, pp. 179–215.

    CAS  PubMed  Google Scholar 

  15. Illanes, A., Cauerhff, A., Wilson, L., and Castro, G.R., Bioresour. Technol., 2012, vol. 115, pp. 48–57.

    Article  CAS  PubMed  Google Scholar 

  16. Hernández-Jústiz, O., Terreni, M., Pagani, G., Garcìa, J., Guisan, J., and Fernandez-Lafuente, R., Enzyme Microb. Technol., 1999, vol. 25, nos. 3–5, pp. 336–343.

    Article  Google Scholar 

  17. WO Patent no. 2004039997, 2004.

  18. Kostadinov, M., Nikolov, A., Tsoneva, N., and Petkov, N., Appl. Biochem. Biotechnol., 1992, vol. 33, no. 3, pp. 177–182.

    Article  CAS  Google Scholar 

  19. Bruggink, A., Roos, E.C., and de Vroom, E., Org. Process Res. Dev., 1998, vol. 2, no. 2, pp. 128–133.

    Article  CAS  Google Scholar 

  20. Hewitt, L., Kasche, V., Lummer, K., Lewis, R.J., Murshudov, G.N., Verma, C.S., Dodson, G.G., and Wilson, K.S., J. Mol. Biol., 2000, vol. 302, no. 4, pp. 887–898.

    Article  CAS  PubMed  Google Scholar 

  21. Alkema, W.B., Hensgens, C.M., Kroezinga, E.H., de Vries, E., Floris, R., van der Laan, J.M., Dijkstra, B.W., and Janssen, D.B., Protein Eng., 2000, vol. 13, no. 12, pp. 857–863.

    Article  CAS  PubMed  Google Scholar 

  22. Srirangan, K., Orr, V., Akawi, L., Westbrook, A., Moo-Young, M., and Chou, C.P., Biotechnol. Adv., 2013, vol. 31, no. 8, pp. 1319–1332.

    Article  CAS  PubMed  Google Scholar 

  23. Grulich, M., Stěpanek, V., and Kyslik, P., Biotechnol. Adv., 2013, vol. 31, no. 8, pp. 1458–1472.

    Article  CAS  PubMed  Google Scholar 

  24. Chandel, A.K., Rao, L.V., Narasu, M.L., and Singh, O.V., Enzyme Microb. Technol., 2008, vol. 42, no. 3, pp. 199–207.

    Article  CAS  Google Scholar 

  25. Senerovic, L., Stankovic, N., Spizzo, P., Basso, A., Gardossi, L., Vasiljevic, B., Ljubijankic, G., Tisminetzky, S., and Degrassi, G., Biotechnol. Bioeng., 2006, vol. 93, no. 2, pp. 344–354.

    Article  CAS  PubMed  Google Scholar 

  26. Panin, N., Sultanov, D., Kirilin, E., Shcherbakova, T., Kudravtsev, P., and Svedas, V., FEBS J., 2013, vol. 280, no. 1, p. 614.

    Google Scholar 

  27. Orr, V., Scharer, J., Moo-Young, M., Honeyman, C.H., Fenner, D., Crossley, L., Suen, S.Y., and Chou, C.P., J. Biotechnol., 2012, vol. 161, no. 1, pp. 19–26.

    Article  CAS  PubMed  Google Scholar 

  28. Palomo, J., Curr. Org. Synth., 2009, vol. 6, no. 1, pp. 1–14.

    Article  CAS  Google Scholar 

  29. Grazú V., López-Gallego F., Montes T., Abian O., Gonzá-lez R., Hermoso J.A., García J.L, Mateo C., Guisán J.M., Process Biochem., 2010, vol. 45, pp. 390–398.

    Article  Google Scholar 

  30. Mateo, C., Abian, O., Fernandez-Lafuente, R., and Guisan, J.M., Enzyme Microb. Technol., 2000, vol. 26, no. 3, pp. 509–515.

    Article  CAS  PubMed  Google Scholar 

  31. Kallenberg, A.I., van Rantwijk, F., and Sheldon, R.A., Adv. Synth. Catal., 2005, vol. 347, nos. 7–8, pp. 905–926.

    Article  CAS  Google Scholar 

  32. Mateo, C., Abian, O., Fernández-Lorente, G., Pedroche, J., Fernandez-Lafuente, R., Guisan, J.M., Tam, A., and Daminati, M., Biotechnol. Prog., vol. 18, no. 3, pp. 629–636.

  33. Fernandez-Lafuente, R., Rosell, C.M., Caanan-Haden, L., Rodes, L., and Guisan, J.M., Enzyme Microb. Technol., 1999, vol. 24, nos. 1–2, pp. 96–103.

    Article  CAS  Google Scholar 

  34. Abian, O., Ferna, G., and Guisa, M., Biotechnol. Prog., 2004, vol. 20, no. 1, pp. 117–121.

    Article  CAS  PubMed  Google Scholar 

  35. Estruch, I., Tagliani, A.R., Guisán, J.M., Fernandez-Lafuente, R., Alcantara, A.R., Toma, L., and Terreni, M., Enzyme Microb. Technol., 2008, vol. 42, no. 2, pp. 121–129.

    Article  CAS  PubMed  Google Scholar 

  36. Wilson, L., Illanes, A., Romero, O., and Vergara, J.M.C., Enzyme Microb. Technol., 2008, vol. 43, no. 6, pp. 442–447.

    Article  CAS  Google Scholar 

  37. Xu, Y., Rosenkranz, S., Weng, C-L., Scharer, J.M., Moo-Young, M., and Chou, C.P., Appl. Microbiol. Biotechnol., 2006, vol. 72, no. 3, pp. 529–536.

    Article  CAS  PubMed  Google Scholar 

  38. Narayanan, N., Hsieh, M-Y., Xu, Y., and Chou, C.P., Biotechnol. Prog., 2005, vol. 22, no. 3, pp. 617–625.

    Article  Google Scholar 

  39. Narayanan, N., Xu, Y., and Chou, C.P., Biotechnol. Prog., 2006, vol. 22, no. 6, pp. 1518–1523.

    Article  CAS  PubMed  Google Scholar 

  40. Vélez, A.M., Silva, A.J., Luperni Horta, A.C., Sargo, C.R., Campani, G., Gonçalves Silva, G., de Lima Camargo Giordano, R., and Zangirolami, T.C., BMC Biotechnol., 2014, vol. 14, no. 1, p. 6.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Ignatova, Z., Enfors, S., Hobbie, M., Taruttis, S., Vogt, C., and Kasche, V., Enzyme Microb. Technol., 2000, vol. 26, nos. 2–4, pp. 165–170.

    Article  CAS  PubMed  Google Scholar 

  42. Scherrer, S., Robas, N., Zouheiry, H., Branlant, G., and Branlant, C., Appl. Microbiol. Biotechnol., 1994, vol. 42, no. 1, pp. 85–91.

    Article  CAS  PubMed  Google Scholar 

  43. Sriubolmas, N., Panbangred, W., Sriurairatana, S., and Meevootisom, V., Appl. Microbiol. Biotechnol., 1997, vol. 47, no. 4, pp. 373–378.

    Article  CAS  PubMed  Google Scholar 

  44. Pan, K-L., Hsiao, H-C., Weng, C-L., Wu, M-S., and Chou, C.P., J. Bacteriol., 2003, vol. 185, no. 10, pp. 3020–3030.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. RF Patent no. 2420581, 2011.

  46. Patent of China no. CN 102296057, 2011.

  47. Mardanov, A.V., Eldarov, M.A., Sklyarenko, A.V., Dumina, M.V., Beletsky, A.V., Yarotsky, S.V., and Ravin, N.V., Genome Announc., 2014, vol. 2, no. 6, p. e01222-14.

    Google Scholar 

  48. El’darov, M.A., Sklyarenko, A.V., Mardanov, A.V., Beletskii, A.V., Dumina, M.V., Medvedeva, N.V., Satarova, D.E., Ravin, N.V., and Yarotskii, S.V., Prikl. Biokhim. Mikrobiol., 2015, vol. 51, no. 5, pp. 465–471.

    Google Scholar 

  49. Kurochkina, V.B. and Nys, P.S., Biocatal. Biotransform., 2002, vol. 20, no. 1, pp. 35–41.

    Article  CAS  Google Scholar 

  50. Margolin, A.L., Shvyadas, V.K., Nys, P.S., Kol’tsova, E.V., Savitskaya, E.M., and Berezin, I.V., Antibiotiki, 1978, vol. 23, no. 2, pp. 114–118.

    CAS  PubMed  Google Scholar 

  51. Margolin, A.L., Svedas, V.K., and Berezin, I.V., Biochim. Biophys. Acta, 1980, vol. 616, no. 2, pp. 283–289.

    Article  CAS  PubMed  Google Scholar 

  52. Švedas, V.K., Margolin, A.L., and Berezin, I.V., Enzyme Microb. Technol., 1980, vol. 2, no. 2, pp. 138–144.

    Article  Google Scholar 

  53. Fernandez-Lafuente, R., Rosell, C.M., and Guisán, J.M., Enzyme Microb. Technol., 1991, vol. 13, no. 11, pp. 898–905.

    Article  CAS  PubMed  Google Scholar 

  54. Fernandez-Lafuente, R., Alvaro, G., Blanco, R.M., and Guisan, J.M., Appl. Biochem. Biotechnol., 1991, vol. 27, no. 3, pp. 277–290.

    Article  CAS  Google Scholar 

  55. Fernandez-Lafuente, R., Rosell, C.M., and Guisan, J.M., Biotechnol. Appl. Biochem., 1996, vol. 24, no. 2, pp. 139–143.

    CAS  PubMed  Google Scholar 

  56. Nys, P.S. and Kurochkina, V.B., Appl. Biochem. Biotechnol., 2000, vol. 88, nos. 1–3, pp. 221–230.

    Article  CAS  Google Scholar 

  57. Fernandez-Lafuente, R., Rosell, C.M., Piatkowska, B., and Guisan, J.M., Enzyme Microb. Technol., 1996, vol. 19, no. 1, pp. 9–14.

    Article  CAS  Google Scholar 

  58. Kim, M.G. and Lee, S.B., J. Mol. Catal., 1996, vol. 1, nos. 3–6, pp. 201–211.

    Article  CAS  Google Scholar 

  59. Rosell, C.M., Terreni, M., Fernandez-Lafuente, R., and Guisan, J.M., Enzyme Microb. Technol., 1998, vol. 23, nos. 1–2, pp. 64–69.

    Article  CAS  Google Scholar 

  60. Kim, M.G. and Lee, S.B., J. Mol. Catal., 1996, vol. 1, no. 2, pp. 71–80.

    Article  CAS  Google Scholar 

  61. Kim, M.G. and Lee, S.B., J. Mol.Catal. B Enzym., 1996, vol. 1, nos. 3–6, pp. 181–190.

    Article  Google Scholar 

  62. Kurochkina, V.B. and Nys, P.S., Antibiot. Khimioter., 1999, vol. 44, no. 5, pp. 12–16.

    CAS  PubMed  Google Scholar 

  63. Ulijn, R.V., De Martin, L., Halling, P.J., Moore, B.D., and Janssen, A.E.M., J. Biotechnol., 2002, vol. 99, no. 3, pp. 215–222.

    Article  CAS  PubMed  Google Scholar 

  64. Nierstrasz, V.A., Schroen, C.G.P.H., Bosma, R., Kroon, P.G., Beeftink, H.H., and Janssen, A.E.M., Biocatal. Biotransform., 1999, vol. 17, no. 3, pp. 209–224.

    Article  CAS  Google Scholar 

  65. Terreni, M., Ubiali, D., Pagani, G., Hernandez-Justiz, O., Fernández-Lafuente, R., and Guisan, J.M., Enzyme Microb. Technol., 2005, vol. 36, nos 5–6, pp. 672–679.

    Article  CAS  Google Scholar 

  66. Kurochkina, V.B. and Sklyarenko, A.V., in Biotechnology State of the Art and Prospects for Development., Zaikov, G.E., Ed., Hauppauge, New York: Nova Science Publishers, 2008, ch. 20, pp. 175–204.

  67. Shaw, S., Shyu, J., Hsieh, Y., and Yeh, H., Enzyme Microb. Technol., 2000, vol. 26, nos. 2–4, pp. 142–151.

    Article  CAS  PubMed  Google Scholar 

  68. Nys, P.S., Kurochkina, V.B., and Libinson, G., in IMACS/IFAC First Symp. Math. Model Simul. Agric. Bio-industries, Brussel, Belgium, 1995, vol. IV, pp. B3–1, B3–5.

    Google Scholar 

  69. Kurochkina, V.B., Larina, E.V., Libinson, G.S., and Nys, P.S., Antibiot. Khimioter., 1994, vol.39, no. 12, pp. 3–7.

    CAS  PubMed  Google Scholar 

  70. Won, J.I., Kim, C.G., Kim, J.H., Lee, J.H., and Jeon, Y.J., Appl. Biochem. Biotechnol., 1998, vol. 69, no. 1, pp. 1–9.

    Article  CAS  PubMed  Google Scholar 

  71. Park, C.B., Lee, S.B., and Ryu, D.D., J. Mol. Catal., 2000, vol. 9, nos. 4–6, pp. 275–281.

    Article  CAS  Google Scholar 

  72. Fernandez-Lafuente, R., Guisán, J., Pregnolato, M., and Terreni, M., Tetrahedron Lett., 1997, vol. 38, no. 26, pp. 4693–4696.

    Article  CAS  Google Scholar 

  73. Hernandez-Justiz, O., Fernandez-Lafuente, R., Guisan, J.M., Negri, P., Pagani, G., and Pregnolato, M., Org. Chem., 1997, vol. 62, no. 26, pp. 9099–9106.

    Article  Google Scholar 

  74. Klesov, A.A., Margolin, A.L., and Shvyadas, V.K., Bioorg. Khim., 1977, vol. 3, no. 5, pp. 654–662.

    CAS  Google Scholar 

  75. RF Patent no. 2210596, 2000.

  76. Terreni, M., Pagani, G., Ubiali, D., Fernández-Lafuente, R., Mateo, C., and Guisan, J.M., Bioorg. Med. Chem. Lett., 2001, vol. 11, no. 18, pp. 2429–2432.

    Article  CAS  PubMed  Google Scholar 

  77. Fernández-Lafuente, R., Rosell, C.M., and Guisan, J.M., Enzyme Microb. Technol., 1998, vol. 23, no. 5, pp. 305–310.

    Article  Google Scholar 

  78. Terreni, M., Tchamkam, J., Sarnataro, U., Rocchietti, S., Fernandez-Lafuente, R., and Guisán, J.M., Adv. Synth. Catal., 2005, vol. 347, no. 1, pp. 121–128.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. V. Sklyarenko.

Additional information

Original Russian Text © A.V. Sklyarenko, M.A. El’darov, V.B. Kurochkina, S.V. Yarotsky, 2015, published in Prikladnaya Biokhimiya i Mikrobiologiya, 2015, Vol. 51, No. 6, pp. 546–560.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sklyarenko, A.V., El’darov, M.A., Kurochkina, V.B. et al. Enzymatic synthesis of β-lactam acids (review). Appl Biochem Microbiol 51, 627–640 (2015). https://doi.org/10.1134/S0003683815060150

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0003683815060150

Keywords

Navigation