Skip to main content
SpringerLink
Log in

O-Acetylhomoserine Sulfhydrylase As a Key Enzyme of Direct Sulfhydrylation in Microbial Methionine Biosynthesis (A Review)

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

Abstract

Methionine biosynthesis in most microorganisms proceeds in two alternative ways. Each pathway is catalyzed by independent enzymes and is tightly regulated by methionine. The transulfurylation pathway involves the formation of a cystathionine, and cysteine acts as a source of sulfur. The enzymes of this metabolic pathway are characterized in detail. The direct sulfhydrylation pathway involves the synthesis of homocysteine with the participation of an inorganic sulfur source directly from O-acetylhomoserine and is predominant in most classes of bacteria. The subject of this review is the properties and functioning of one of the least studied enzymes of the direct sulfhydrylation pathway—O-acetylhomoserine sulfhydrylase. A deep understanding of the mechanisms controlling the substrate and reaction specificity of O-acetylhomoserine sulfhydrylase is a necessary step in the rational redesign of the enzyme in order to create a promising catalyst for the synthesis of methionine and its derivatives, as well as, in combination with crystallographic data, for the development of new antimicrobial compounds based on effective enzyme inhibitors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

REFERENCES

  1. Cavuoto, P. and Fenech, M.F., Cancer Treat. Rev., 2012, vol. 38, pp. 726–736.

    Article  CAS  PubMed  Google Scholar 

  2. Finkelstein, J.D., J. Nutr. Biochem., 1990, vol. 1, pp. 228–237.

    Article  CAS  PubMed  Google Scholar 

  3. Stipanuk, M.H., Annu. Rev. Nutr., 2004, vol. 24, pp. 539–577.

    Article  CAS  PubMed  Google Scholar 

  4. Locasale, J.W., Nat. Rev. Cancer, 2013, vol. 13, pp. 572–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Neubauer, C. and Landecker, H., Lancet Planet Health, 2021, vol. 5, pp. 560–569.

    Article  Google Scholar 

  6. Francois, J.M., Biotechnol. Adv., 2023, vol. 19, p. 108259. https://doi.org/10.1016/j.biotechadv.2023.108259

    Article  CAS  Google Scholar 

  7. Born, T.L. and Blanchard, J.S., Biochemistry, 1999, vol. 38, pp. 14416–14423.

    Article  CAS  PubMed  Google Scholar 

  8. Clausen, T., Huber, R., Laber, B., Pohlenz, H.D., and Messerschmidt, A., J. Mol. Biol., 1996, vol. 262, pp. 202–224.

    Article  CAS  PubMed  Google Scholar 

  9. Ferla, M.P. and Patrick, W.M., Microbiology, 2014, vol. 160, pp. 1571–1584.

    Article  CAS  PubMed  Google Scholar 

  10. Foglino, M., Borne, F., Bally, M., Ball, G., and Patte, J., Microbiology, 1995, vol. 141, pp. 431–439.

    Article  CAS  PubMed  Google Scholar 

  11. Vermeij, P. and Kertesz, M.A., J. Bacteriol., 1999, vol. 181, pp. 5833–5837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hwang, B.J., Kim, Y., Kim, H.B., Hwang, H.J., Kim, J.H., and Lee, H.S., Mol. Cells, 1999, vol. 9, pp. 300–308.

    Article  CAS  PubMed  Google Scholar 

  13. Hwang, B.J., Yeom, H.J., Kim, Y., and Lee, H.S., J. Bacteriol., 2002, vol. 184, pp. 1277–1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee, H. and Hwang, B., Appl. Microbiol. Biotechnol., 2003, vol. 62, pp. 459–467.

    Article  CAS  PubMed  Google Scholar 

  15. Belfaiza, J., Martel, A., Margarita, D., and Saint Girons, I., J. Bacteriol., 1998, vol. 180, pp. 250–255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Picardeau, M., Bauby, H., and Saint Girons, I., FEMS Microbiol. Lett., 2003, vol. 225, pp. 257–262.

    Article  CAS  PubMed  Google Scholar 

  17. Yamagata, S., Ichioka, K., Goto, K., Mizuno, Y., and Iwama, T., J. Bacteriol., 2001, vol. 183, pp. 2086–2092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shimizu, H., Yamagata, S., Masui, R., Inoue, Y., Shibata, T., Yokoyama, S., et al., Biochim. Biophys. Acta, 2001, vol. 1549, pp. 61–72.

    Article  CAS  PubMed  Google Scholar 

  19. Yoshida, Y., Negishi, M., and Nakano, Y., FEMS Microbiol. Lett., 2003, vol. 221, pp. 277–284.

    Article  CAS  PubMed  Google Scholar 

  20. Bairoch, A., Nucleic Acids Res., 2000, vol. 28, pp. 304–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. UniProt Consortium, Nucleic Acids Res., 2023, vol. 51, no. D1, pp. D523–D531.

    Article  Google Scholar 

  22. Auger, S., Yuen, W.H., Danchin, A., and Martin-Verstraete, I., Microbiology, 2002, vol. 148, pp. 507–518.

    Article  CAS  PubMed  Google Scholar 

  23. Farsi, A., Lodha, P.H., Skanes, J.E., Los, H., Kalidindi, N., and Aitken, S.M., Biochem. Cell Biol., 2009, vol. 87, pp. 445–457.

    Article  CAS  PubMed  Google Scholar 

  24. Shim, J., Shin, Y., Lee, I., and Kim, S.Y., Adv. Biochem. Eng. Biotechnol., 2017, vol. 159, pp. 153–177.

    CAS  PubMed  Google Scholar 

  25. Aitken, S.M., Kim, D.H., and Kirsch, J.F., Biochemistry, 2003, vol. 42, pp. 11297–11306.

    Article  CAS  PubMed  Google Scholar 

  26. Omura, H., Ikemoto, M., Kobayashi, M., Shimizu, S., Yoshida, T., and Nagasawa, T., J. Biosci. Bioeng., 2003, vol. 96, pp. 53–58.

    Article  CAS  PubMed  Google Scholar 

  27. Kulikova, V.V., Revtovich, S.V., Bazhulina, N.P., Anufrieva, N.V., Kotlov, M.I., Koval, V.S., et al., IUBMB Life, 2019, vol. 71, pp. 1815–1823.

    Article  CAS  PubMed  Google Scholar 

  28. Brewster, J.L., Pachl, P., McKellar, J.L., Selmer, M., Squire, C.J., and Patrick, W.M., J. Biol. Chem., 2021, vol. 296, p. 100797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ferla, M.P., Brewster, J.L., Hall, K.R., Evans, G.B., and Patrick, W.M., Mol. Microbiol., 2017, vol. 105, pp. 508–524.

    Article  CAS  PubMed  Google Scholar 

  30. Krishnamoorthy, K. and Begley, T.P., J. Am. Chem. Soc., 2011, vol. 133, pp. 379–386.

    Article  CAS  PubMed  Google Scholar 

  31. Brzywczy, J., Yamagata, S., and Paszewski, A., Acta Biochim. Pol., 1993, vol. 40, pp. 421–428.

    Article  CAS  PubMed  Google Scholar 

  32. Bolten, C.J., Schroder, H., Dickschat, J., and Wittmann, C.J., Microbiol. Biotechnol., 2010, vol. 20, pp. 1196–1203.

    Article  CAS  Google Scholar 

  33. Ma, Y., Biava, H., Contestabile, R., Budisa, N., and di Salvo, M.L., Molecules, 2014, vol. 19, pp. 1004–1022.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dauplais, M., Bierla, K., Maizeray, C., Lestini, R., Lobinski, R., Pierre Plateau, P., et al., Int. J. Mol. Sci., 2021, vol. 22, p. 2241. https://doi.org/10.3390/ijms22052241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Iwama, T., Hosokawa, H., Lin, W., Shimizu, H., Kawai, K., and Yamagata, S., Biosci. Biotechnol. Biochem., 2004, vol. 68, pp. 1357–1361.

    Article  CAS  PubMed  Google Scholar 

  36. Yamagata, S., J. Biochem., 1971, vol. 70, pp. 1035–1045.

    Article  CAS  PubMed  Google Scholar 

  37. Kulikova, V.V., Anufrieva, N.V., Kotlov, M.I., Morozova, E.A., Koval, V.S., Belyi, Y.F., et al., Protein Expr. Purif., 2021, vol. 180, p. 105810.

    Article  CAS  PubMed  Google Scholar 

  38. Aitken, S.M. and Kirsch, J.F., Arch. Biochem. Biophys., 2005, vol. 433, pp. 166–175.

    Article  CAS  PubMed  Google Scholar 

  39. Brzovic, P., Holbrook, E.L., Greene, R.C., and Dunn, M., Biochemistry, 1990, vol. 29, pp. 442 – 451.

    Article  CAS  PubMed  Google Scholar 

  40. Kerr, D.S., J. Biol. Chem., 1971, vol. 246, pp. 95–102.

    Article  CAS  PubMed  Google Scholar 

  41. Hwang, B.J., Park, S.D., Kim, Y., Kim, P., and Lee, H.S., J. Microbiol. Biotechnol., 2007, vol. 17, pp. 1010–1017.

    CAS  PubMed  Google Scholar 

  42. Messerschmidt, A., Worbs, M., Steegborn, C., Wahl, M.C., Huber, R., Laber, B., and Clausen, T., Biol. Chem., 2003, vol. 384, pp. 373–386.

    Article  CAS  PubMed  Google Scholar 

  43. Aitken, S.M., Lodha, P.H., and Morneau, D.J.K., Biochim. Biophys. Acta, 2011, vol. 814, pp. 1511–1517.

    Article  Google Scholar 

  44. Lodha, P.H., Jaworski, A.F., and Aitken, S.M., Protein Sci., 2010, vol. 19, pp. 383–391.

    Article  CAS  PubMed  Google Scholar 

  45. Kulikova, V.V., Revtovich, C.V., Lyfenko, A.D., Morozova, E.A., Koval’, V.S., Bazhulina, N.P., et al., Biochemistry (Moscow), 2023, vol. 88, pp. 600–609.

    CAS  PubMed  Google Scholar 

  46. Clausen, T., Huber, R., Laber, B., Pohlenz, H.-D., and Messerschmidt, A., J. Mol. Biol., 1996, vol. 262, pp. 202–224.

    Article  CAS  PubMed  Google Scholar 

  47. Clausen, T., Huber, R., Messerschmidt, A., Pohlenz, H.D., and Laber, B., Biochemistry, 1997, vol. 36, pp. 12633–12643.

    Article  CAS  PubMed  Google Scholar 

  48. Clausen, T., Huber, R., Prade, L., Wahl, M.C., and Messerschmidt, A., EMBO J., 1998, vol. 23, pp. 6827–6838.

    Article  Google Scholar 

  49. Steegborn, C., Messerschmidt, A., Laber, B., Streber, W., Huber, R., and Clausen, T., J. Mol. Biol., 1999, vol. 290, pp. 983–996.

    Article  CAS  PubMed  Google Scholar 

  50. Breitinger, U., Clausen, T., Ehlert, S., Huber, R., Laber, B., Schmidt, F., et al., Plant Physiol., 2001, vol. 126, pp. 631–642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tran, T., Krishnamoorthy, K., Begley, T.P., and Ealick, S.E., Acta Cryst., 2011, vol. D67, pp. 831–838.

    Google Scholar 

  52. Baugh, L., Phan, I., Begley, D.W., Clifton, M.C., Armour, B., et al., Tuberculosis (Edinb.), 2015, vol. 95, pp. 142–148.

    Article  CAS  PubMed  Google Scholar 

  53. Wahl, M.C., Huber, R., Prade, L., Marinkovic, S., Messerschmidt, A., and Clausen, T., FEBS Lett., 1997, vol. 414, pp. 492–496.

    Article  CAS  PubMed  Google Scholar 

  54. Revtovich, S.V., Morozova, E.A., Anufrieva, N.V., Kotlov, M.I., Belyi, Yu.F., and Demidkina, T.V., Dokl. Biochem. Biophys., 2012, vol. 445, no. 2, pp. 187–193.

    Article  CAS  PubMed  Google Scholar 

  55. Anufrieva, N.V., Morozova, E.A., Revtovich, S.V., Bazhulina, N.P., Timofeev, V.P., Tkachev, Ya.V., et al., Acta Nat., 2022, vol. 14, pp. 4–15.

    Google Scholar 

  56. Ngo, H.-P.-T., Kim, J.-K., Kim, S.-H., Pham, T.-V., Tran, T.-H., Nguyen, D.-D., Kim, J.-G., Chung, S., Ahn, Y.-J., and Kang, L.-W., Acta Crystallogr. Sect. F, 2012, vol. 68, pp. 1515–1517.

    Article  CAS  Google Scholar 

  57. Mondal, S., Das, Y.B., and Chatterjee, S.P., Folia Microbiol. (Praha), 1996, vol. 41, pp. 465–472.

    Article  CAS  PubMed  Google Scholar 

  58. Hacham, Y., Gophna, U., and Amir, R., Mol. Biol. Evol., 2003, vol. 20, pp. 1513–1520.

    Article  CAS  PubMed  Google Scholar 

  59. Gophna, U., Bapteste, E., Doolittle, W.F., Biran, D., and Ron, E.Z., Gene, 2005, vol. 1, pp. 48–57.

    Article  Google Scholar 

  60. Jankowski, J., Ognik, K., Konieczka, P., and Mikulski, D., Poult. Sci., 2020, vol. 99, pp. 4730–4740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Konieczka, P., Tykałowski, B., Ognik, K., Kinsner, M., Szkopek, D., Wojcik, M., et al., Vet. Res., 2022, vol. 26, p. 59. https://doi.org/10.1186/s13567-022-01080-7

    Article  CAS  Google Scholar 

  62. Navik, U., Sheth, V.G., Khurana, A., Jawalekar, S.S., Allawadhi, P., Gaddam, R.R., Bhatti, J.S., and Tikoo, K., Ageing Res. Rev., 2021, vol. 72, p. 101500.

    Article  CAS  PubMed  Google Scholar 

  63. Li, Y., Cong, H., Liu, B., Song, J., Sun, X., Zhang, J., and Yang, Q., Antonie Van Leeuwenhoek, 2016, vol. 109, pp. 1185–1197.

    Article  CAS  PubMed  Google Scholar 

  64. Kumar, D. and Gomes, J., Biotechnol Adv., 2005, vol. 23, p. 41.

    Article  CAS  PubMed  Google Scholar 

  65. Hashimoto, S.-I., Adv. Biochem. Eng. Biotechnol., 2017, vol. 159, pp. 15–34.

    PubMed  Google Scholar 

  66. Eliot, A.C. and Kirsch, J.F., Annu. Rev. Biochem., 2004, vol. 73, pp. 383–415.

    Article  CAS  PubMed  Google Scholar 

  67. Paiardini, A., Contestabile, R., Buckle, A.M., and Cellini, B., Biomed. Res. Int., 2014, p. 856076. https://doi.org/10.1155/2014/856076

  68. Omura, H., Ikemoto, M., Kobayashi, M., Shimizu, S., Yoshida, T., and Nagasawa, T., J. Biosci. Bioeng., 2003, vol. 96, pp. 53–58.

    Article  CAS  PubMed  Google Scholar 

  69. Di Salvo, M.L., Fesko, K., Phillips, R.S., and Contestabile, R., Front. Bioeng. Biotechnol., 2020, vol. 8, p. 52.https://doi.org/10.3389/fbioe.2020.00052

  70. Ravikumar, Y., Nadarajan, S.P., Yoo, T.H., Lee, C.-S., and Yun, H., Biotechnol. J., 2015, vol. 10, pp. 1862–1876.

    Article  CAS  PubMed  Google Scholar 

  71. Kovaleva, G.Yu. and Gel’fand, M.S., Mol. Biol. (Moscow), 2007, vol. 41, no. 1, pp. 126–136.

    Article  CAS  Google Scholar 

  72. Park, S.D., Lee, J.Y., Sim, S.Y., Kim, Y., and Lee, H.S., Metab. Eng., 2007, vol. 9, pp. 327–336.

    Article  CAS  PubMed  Google Scholar 

  73. Han, G., Hu, X., Qin, T., Li, Y., and Wang, X., Enzyme Microb. Technol., 2016, vol. 83, pp. 14–21.

    Article  CAS  PubMed  Google Scholar 

  74. Qin, T., Hu, X., Hu, J., and Wang, X., Biotechnol. Appl. Biochem., 2015, vol. 62, p. 563.

    Article  CAS  PubMed  Google Scholar 

  75. Gruzdev, N., Hacham, Y., Haviv, H., Stern, I., Gabay, M., Bloch, I., et al., Microb. Cell Fact., 2023, vol. 22.

  76. Wang, H., Li, Y., Che, Y., Yang, D., Wang, Q., Yang, H., et al., J. Agric. Food Chem., 2021, vol. 69, pp. 7932–7937.

    Article  CAS  PubMed  Google Scholar 

  77. Kim, S.I., Sin, I.Yu., Seo, Ch.I., Son, S.K., Kheo, I.K., Li, Kh.D., Kim, D.E., Kim, Kh.A., Bae, D.I., and Na, K.Kh., RF Patent No. 2 573 928 C2, 2011.

Download references

Funding

This work was supported by the Russian Science Foundation, project no. 22-24-00255.

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    V. V. Kulikova, E. A. Morozova, A. D. Lyfenko, V. S. Koval, N. V. Anufrieva, P. N. Solyev & S. V. Revtovich

Authors
  1. V. V. Kulikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. A. Morozova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. D. Lyfenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. S. Koval
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. V. Anufrieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. N. Solyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. V. Revtovich
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

V.V. Kulikova wrote the manuscript, E.A. Morozova and A.D. Lyfenko searched and analyzed the data, V.S. Koval designed the figures, N.V. Anufrieva created the tables, P.N. Solyev supervised the project, S.V. Revtovich designed and directed the project.

Corresponding author

Correspondence to V. V. Kulikova.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This work does not contain any studies involving human and animal subjects.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kulikova, V.V., Morozova, E.A., Lyfenko, A.D. et al. O-Acetylhomoserine Sulfhydrylase As a Key Enzyme of Direct Sulfhydrylation in Microbial Methionine Biosynthesis (A Review). Appl Biochem Microbiol 60, 359–371 (2024). https://doi.org/10.1134/S0003683824603561

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0003683824603561

Keywords:

Search

Navigation