O-Acetylhomoserine Sulfhydrylase as a Key Enzyme of Direct Sulfhydrylation in Microbial Methionine Biosynthesis

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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 s 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.

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About the authors

V. V. Kulikova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Author for correspondence.
Email: vitviku@yandex.ru
Russian Federation, Moscow

E. A. Morozova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

A. D. Lyfenko

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

V. S. Koval

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

N. V. Anufrieva

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

P. N. Solyev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

S. V. Revtovich

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vitviku@yandex.ru
Russian Federation, Moscow

References

  1. Cavuoto P., Fenech M.F. // Cancer Treat. Rev. 2012. V. 38. P. 726–736.
  2. Finkelstein J.D. // J. Nutr. Biochem. 1990. V. 1. P. 228–237.
  3. Stipanuk M.H. // Annu. Rev. Nutr. 2004. V. 24. P. 539–577.
  4. Locasale J.W. // Nat. Rev. Cancer. 2013. V. 13. P. 572–583.
  5. Neubauer C., Landecker H. // Lancet Planet Health. 2021. V. 5. P. 560–569.
  6. François J.M. // Biotechnol. Adv. 2023. V. 19. P. 108259. https://doi.org/10.1016/j.biotechadv.2023.108259
  7. Born T.L., Blanchard J.S. // Biochemistry. 1999. V. 38. P. 14416–14423.
  8. Clausen T., Huber R., Laber B., Pohlenz H.D., Messerschmidt A. // J. Mol. Biol. 1996.V. 262. P. 202–224.
  9. Ferla M.P., Patrick W.M. // Microbiology. 2014. V. 160. P. 1571–1584.
  10. Foglino M., Borne F., Bally M., Ball G., Patte J. // Microbiology. 1995. V. 141. P. 431–439.
  11. Vermeij P., Kertesz M.A. // J. Bacteriol. 1999. V. 181. P. 5833–5837.
  12. Hwang B.J., Kim Y., Kim H.B., Hwang H.J., Kim J.H., Lee H.S. // Mol. Cells. 1999. V. 9. P. 300–308.
  13. Hwang B.J., Yeom H.J., Kim Y., Lee H.S. // J. Bacteriol. 2002. V. 184. P. 1277–1286.
  14. Lee H., Hwang B. // Appl. Microbiol. Biotechnol. 2003. V. 62. P. 459–467.
  15. Belfaiza J., Martel A., Margarita D., Saint Girons I. // J. Bacteriol. 1998. V. 180. P. 250–255.
  16. Picardeau M., Bauby H., Saint Girons I. // FEMS Microbiol. Lett. 2003. V. 225. P. 257–262.
  17. Yamagata S., Ichioka K., Goto K., Mizuno Y., Iwama T. // J. Bacteriol. 2001. V. 183. P. 2086–2092.
  18. Shimizu H., Yamagata S., Masui R., Inoue Y., Shibata T., Yokoyama S. et al. // Biochim. Biophys. Acta. 2001. V. 1549. P. 61–72.
  19. Yoshida Y., Negishi M., Nakano Y. // FEMS Microbiol. Lett. 2003. V. 221. P. 277–284.
  20. Bairoch A. // Nucleic Acids Res. 2000. V. 28. P. 304–305.
  21. UniProt Consortium // Nucleic Acids Res. 2023. V. 51 (D1). D523–D531.
  22. Auger S., Yuen W.H., Danchin A., Martin-Verstraete I. // Microbiology. 2002. V. 148. P. 507–518.
  23. Farsi A., Lodha P.H., Skanes J.E., Los H., Kalidindi N., Aitken S.M. // Biochem. Cell Biol. 2009. V. 87. P. 445–457.
  24. Shim J., Shin Y., Lee I., Kim S.Y. // Adv. Biochem. Eng. Biotechnol. 2017. V. 159. P. 153–177.
  25. Aitken S.M., Kim D.H., Kirsch J.F. // Biochemistry. 2003. V. 42. P. 11297–11306.
  26. Omura H., Ikemoto M., Kobayashi M., Shimizu S., Yoshida T., Nagasawa T. // J. Biosci. Bioeng. 2003. V. 96. P. 53–58.
  27. Kulikova V.V., Revtovich S.V., Bazhulina N.P., Anufrieva N.V., Kotlov M.I., Koval V.S. et al. // IUBMB Life. 2019. V. 71. P. 1815–1823.
  28. Brewster J.L., Pachl P., McKellar J.L., Selmer M., Squire C.J., Patrick W.M. // J. Biol. Chem. 2021. V. 296. P. 100797.
  29. Ferla M.P., Brewster J.L., Hall K.R., Evans G.B., Patrick W.M. // Mol. Microbiol. 2017. V. 105. P. 508–524.
  30. Krishnamoorthy K., Begley T.P. // J. Am. Chem. Soc. 2011. V.133. P. 379–386.
  31. Brzywczy J., Yamagata S., Paszewski A. // Acta Biochim. Pol. 1993. V. 40. P. 421–428.
  32. Bolten C.J., Schröder H., Dickschat J., Wittmann C.J. // Microbiol. Biotechnol. 2010. V. 20. P. 1196–1203.
  33. Ma Y., Biava H., Contestabile R., Budisa N., di Salvo M.L. // Molecules. 2014. V. 19. P. 1004–1022.
  34. Dauplais M., Bierla K., Maizeray C., Lestini R., Lobinski R., Pierre Plateau P. et al. // Int. J. Mol. Sci. 2021. V. 22: 2241. https://doi.org/10.3390/ijms22052241.
  35. Iwama T., Hosokawa H., Lin W., Shimizu H., Kawai K., Yamagata S. // Biosci. Biotechnol. Biochem. 2004. V. 68. P. 1357–1361.
  36. Yamagata S. // J. Biochem. 1971. V. 70. P. 1035–1045.
  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. V. 180. P. 105810.
  38. Aitken S.M., Kirsch J.F. // Arch. Biochem. Biophys. 2005. V. 433. P. 166–175.
  39. Brzovic P., Holbrook E.L., Greene R.C., Dunn M. // Biochemistry. 1990. V. 29. P. 442–451.
  40. Kerr D.S. // J. Biol. Chem. 1971. V. 246. P. 95–102.
  41. Hwang B.J., Park S.D, Kim Y., Kim P., Lee H.S. // J. Microbiol. Biotechnol. 2007. V. 17. P. 1010–1017.
  42. Messerschmidt A., Worbs M., Steegborn C., Wahl M. C., Huber R., Laber B., Clausen T. // Biol. Chem. 2003. V. 384. P. 373–386.
  43. Aitken S.M., Lodha P.H., Morneau, D.J.K. // Biochim. Biophys. Acta. 2011. V. 814. P. 1511–1517.
  44. Lodha P.H., Jaworski A.F., Aitken S.M. // Protein Sci. 2010. V. 19. P. 383–391.
  45. Куликова В.В., Ревтович C.В., Лыфенко А.Д., Морозова Е.А., Коваль В.С., Бажулина Н.П. и др. // Биохимия. 2023. T. 88. C. 737–747.
  46. Clausen T., Huber R., Laber B., Pohlenz H.-D., Messerschmidt A. // J. Mol. Biol. 1996. V. 262. P. 202–224.
  47. Clausen T., Huber R., Messerschmidt A., Pohlenz H.D., Laber B. // Biochemistry. 1997. V. 36. P. 12633–12643.
  48. Clausen T., Huber R., Prade L., Wahl M.C., Messerschmidt A. // EMBO J. 1998. V. 23. P. 6827–6838.
  49. Steegborn C., Messerschmidt A., Laber B., Streber W., Huber R., Clausen T. // J. Mol. Biol. 1999. V. 290. P. 983–996.
  50. Breitinger U., Clausen T., Ehlert S., Huber R., Laber B., Schmidt F. et al. // Plant Physiol. 2001. V. 126. P. 631–642.
  51. Tran T.., Krishnamoorthy K., Begley T.P., Ealick S.E. // ActaCryst. 2011. V. D67. P. 831–838.
  52. Baugh L., Phan I., Begley D.W., Clifton M.C., Armour B. et al. // Tuberculosis (Edinb). 2015. V. 95. P. 142–148.
  53. Wahl M.C., Huber R., Prade L., Marinkovic S., Messerschmidt A., Clausen T. // FEBS Lett. 1997. V. 414. P. 492–496.
  54. Ревтович С.В., Морозова Е.А., Ануфриева Н.В., Котлов М.И., Белый Ю.Ф., Демидкина Т.В. // Докл. АН. 2012. Т. 445. № 2. С. 214–220.
  55. Ануфриева Н.В., Морозова Е.А., Ревтович С.В., Бажулина Н.П., Тимофеев В.П., Ткачев Я.В. и др. // Acta Naturae. 2022. T. 14. C. 4–15.
  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., Kang L.-W. // Acta Crystallogr. Sect. F. 2012. V. 68. P. 1515–1517.
  57. Mondal S., Das Y.B., Chatterjee S.P. // Folia Microbiol (Praha). 1996. V. 41. P. 465–472.
  58. Hacham Y., Gophna, U., Amir, R. // Mol. Biol. Evol. 2003. V. 20. P. 1513–1520.
  59. Gophna U., Bapteste E., Doolittle W.F., Biran D., Ron E.Z. // Gene. 2005. V. 1. P. 48–57.
  60. Jankowski J., Ognik K., Konieczka P., Dariusz Mikulski D. // Poult. Sci. 2020. V. 99. P. 4730–4740.
  61. Konieczka P., Tykałowski B., Ognik K., Kinsner M., Szkopek D., Wójcik et al. // Vet. Res. 2022. V. 26 P. 59. https://doi.org/10.1186/s13567-022-01080-7.
  62. Navik U., Sheth V.G., Khurana A., Jawalekar S.S., Allawadhi P., Gaddam R.R., Bhatti J.S., Tikoo K. // Ageing Res. Rev. 2021. V. 72. P. 101500.
  63. Li Y., Cong H., Liu B., Song J., Sun X., Zhang J., Yang Q. // Antonie Van Leeuwenhoek. 2016. V. 109. P. 1185–1197.
  64. Kumar D., Gomes J. // Biotechnol Adv. 2005. V. 23. P. 41–61.
  65. Hashimoto S.-I. // Adv. Biochem. Eng. Biotechnol. 2017. V. 159. P. 15–34.
  66. Eliot A. C., Kirsch J. F. // Annu. Rev. Biochem. 2004. V. 73. P. 383–415.
  67. Paiardini A., Contestabile R., Buckle A.M., Cellini B. // Biomed. Res. Int. 2014. Article ID856076. https://doi.org/10.1155/2014/856076.
  68. Omura H., Ikemoto M., Kobayashi M., Shimizu S., Yoshida T., Nagasawa T. // J. Biosci. Bioeng. 2003. V. 96. P. 53–58.
  69. Di Salvo M.L., Fesko K., Phillips R.S., Contestabile R. // Front. Bioeng. Biotechnol. 2020. V. 8. Article ID52.https://doi.org/10.3389/fbioe.2020.00052.
  70. Ravikumar Y., Nadarajan S.P., Yoo T.H., Lee C.-S., Yun H. // Biotechnol. J. 2015. V. 10. P. 1862–1876.
  71. Ковалева Г.Ю., Гельфанд М.С. // Молекулярная биология. 2007. Т. 41. № 1. C. 139–150.
  72. Park S.D., Lee J.Y., Sim S.Y., Kim Y., Lee H.S. // Metab. Eng. 2007. V. 9. P. 327–336.
  73. Han G., Hu X., Qin T., Li Y., Wang X. // Enzyme Microb. Technol. 2016. V. 83. P. 14–21.
  74. Qin T., Hu X., Hu J., Wang X. // Biotechnol. Appl. Biochem. 2015. V. 62. P. 563–573.
  75. Gruzdev N., Hacham Y., Haviv H., Stern I., Gabay M., Bloch I. et al. // Microbial Cell Factories. 2023. V. 22:151 https://doi.org/10.1186/s12934-023-02150-x
  76. Wang H., Li Y., Che Y., Yang D., Wang Q., Yang H. et al. // J. Agric. Food Chem. 2021. V. 69. P. 7932–7937.
  77. Ким С.Й., Син Й.Ю., Сео Ч.И., Сон С.К., Хео И.К., Ли Х.Д., Ким Д.Е., Ким Х.А., Бае Д.Й., На К.Х. Патент РФ 2011. № 2 573 928 C2.

Supplementary files

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2. Fig. 1. Biosynthesis of methionine in microorganisms.

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3. Fig. 2. Scheme of the γ-substitution reaction catalyzed by OAHS.

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4. Fig. 3. Alignment of OAHS amino acid sequences from Campylobacter jejuni (Cje; 4OC9), Mycobacterium marinum (Mma; B2HDS7), T. maritima (Tma; Q9WZY4), T. thermophilus (Tth1; Q5SK88 and Tth2; Q5SJ58), W. succinogenes (Wsu; Q7M9C8), Clostridium novyi (Cno; A0A5B8NEI4), Clostridium difficile (Cdi; A0A1L7H895), L. meyeri (Lme; P94890), M. tuberculosis (Mtu; L7N4M1), Saccharomyces cerevisiae (Sce; P06106). Conserved residues are marked in black. Enzyme sequences with known 3D structures are marked with a vertical line; triangles mark the functional residues of the active center.

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5. Fig. 4. Proposed mechanism of the OAHS-catalyzed γ-substitution reaction.

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6. Fig. 5. Tetrameric organization of OAHS using the structure of the enzyme from T. thermophilus as an example (pdb code 2ctz).

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7. Fig. 6. Superposition of polypeptide chains (a) of spatial structures of OASH from different microorganisms: C. jejuni OAHS (pdb code 4OC9) – dark blue, M. marinum OASH (pdb code 4KAM) – light blue, T. maritima OASH (pdb code 7KB1) – purple, T. thermophilus OASH (pdb code 2CTZ) – green, T. thermophilus OASH (pdb code 2CB1) – dark green, W. succinogenes OASH (pdb code 3RI6) – orange; (b) spatial structures of enzymes of the CBL subclass: T. maritima OASH (pdb code 7KB1) – orange, Citrobacter freundii methionine γ-lyase MGL (pdb code 2RFV) – dark blue, Arabidopsis thaliana CBL (pdb code 1IBJ) – light blue, Nicotiana tabacum CGS (pdb code 1I41) – green, S. cerevisiae cystathionine γ-lyase (pdb code 1N8P) – purple. The unique fragment characteristic of the OASH enzyme is highlighted in oval.

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8. Fig. 7. Scheme of interactions of α,β-unsaturated ketimine with amino acid residues of the active center of OAHS (T. maritima numbering). Amino acid residues of the neighboring monomer are indicated by an asterisk. Dashed lines show hydrogen bonds, and dotted lines show π-interactions.

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9. Fig. 8. Absorption spectra of OAHS from C. difficile (a) and C. novyi (b) at pH 7.5.

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