Synthesis of Serine, Glycine, Cysteine, and Methionine

Frank J. Grundy; Tina Μ. Henkin

doi:10.1128/9781555817992.ch18

Chapter 18 : Synthesis of Serine, Glycine, Cysteine, and Methionine

Authors: Frank J. Grundy, Tina Μ. Henkin

Content Type: Monograph

Publication Year: 2002

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555817992

Chapter DOI: 10.1128/9781555817992.ch18

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Abstract:

Methionine and cysteine are the two sulfur-containing amino acids, and cysteine biosynthesis represents the primary pathway for incorporation of organic sulfur into cellular components. Synthesis of the sulfur-containing amino acids is connected to central metabolism through the precursors serine, glycine, and homoserine. In addition to its general function as a component of proteins, methionine is specifically required for translation initiation and is crucial to a variety of methyltransferase reactions, both as a precursor of S-adenosylmethionine (SAM) and in tetrahydrofolate (THF) metabolism. The primary pathway for glycine generation in bacteria is through the interconversion of serine and glycine by L-serine hydroxymethyltransferase, encoded by glyA. Conversion of serine to glycine also provides N5,N10-methylene-THF, which is reduced by N5,N10-methylene-THF reductase to generate N5-methyl-THF for use in the conversion of homocysteine to methionine; this step regenerates the THF required for glycine production. In the major route of methionine biosynthesis, the backbone of methionine is derived from homoserine, and the sulfur moiety is derived from cysteine. Utilization of SAM as methyl donor results in formation of S-adenosylhomocysteine (SAH), whereas during polyamine biosynthesis SAM is first decarboxylated by the speD gene product, after which spermidine synthase catalyzes its reaction with putrescine to yield spermidine and methylthioadenosine (MTA). Homocysteine derived from SAH can be reconverted to methionine by methionine synthase, while methylthioribose (MTR) in Escherichia coli is excreted. The coupling of genomic sequence data with information about known physiological properties of the organism and regulatory insights provides a unique opportunity to identify putative genes and pathways.

Citation: Grundy F, Henkin T. 2002. Synthesis of Serine, Glycine, Cysteine, and Methionine, p 245-254. In Sonenshein A, Losick R, Hoch J (ed), Bacillus subtilis and Its Closest Relatives. ASM Press, Washington, DC. doi: 10.1128/9781555817992.ch18

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Synthesis of Serine, Glycine, Cysteine, and Methionine

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FIGURE 1

Cysteine and methionine metabolic pathways. Genes that are linked to S-box or T-box regulatory elements are shown with a boxed S or T, respectively. The amino acid corresponding to the T-box element specifier sequence is shown to the right in single-letter abbreviation. An asterisk to the left of the boxed S or Τ indicates genes that contain S- or T-box leaders in other gram-positive species (see Table 1 ). All other genes are those of B. subtilis except those in parentheses, which are Escherichia coli genes that have no apparent homologs in B. subtilis. B. subtilis genes starting with “y” are genes whose function has not been experimentally established. hipO was previously named only on the basis of homology. Genes in brackets are second copies of genes whose function has already been investigated. Only ATPs that contribute more than a phosphate moiety are shown. Abbreviations not found in the text: α-KB, α-ketobutyrate; O-AH, O-acetylhomoserine; KMTB, ketomethylthiobutyrate.

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FIGURE 1

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FIGURE 2

S-box and T-box transcription termination control mechanisms. (A) S-box system. During growth in the presence of methionine, a regulatory factor (dotted ellipse) binds to the upstream stem-loop of the leader RNA in response to methonine or some other effector (box). Binding stabilizes the anti-antiterminator form of the leader, preventing formation of the antiterminator form, permitting termination. When methionine is limiting, the anti-antiterminator is destabilized, permitting formation of the antiterminator and transcription of the downstream genes (arrow). All genes in the family respond to methionine availability. T, terminator; AT, antiterminator; AAT, anti-antiterminator. (B) T-box system. When charging of the cognate tRNA is high, the charged tRNA (with box representing the amino acid) binds by codon-anticodon pairing to the specifier sequence in the leader RNA but is unable to stabilize the antiterminator so that the terminator forms. Uncharged tRNA can interact with both the specifier sequence and the side-bulge of the antiterminator, stabilizing the antiterminator and preventing termination. Each gene in the family responds individually to the charging ratio of its cognate tRNA, with specificity primarily directed by the identity of the codon at the position of the specifier sequence. S, specifier sequence; Τ, T-box sequence, which forms the 5′ part of the antiterminator.

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FIGURE 2

References

/content/book/10.1128/9781555817992.chap18

1. Anagnostopoulos, C.,, P. J. Piggot,, and J. A. Hoch,. 1993. The genetic map of Bacillus subtilis, p. 425– 461. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics. American Society for Microbiology, Washington, D.C.

2. Beck, R.,, E. Raux,, C. Thermes,, A. Rambach,, and M. Warren. 1997. CbiX: a novel metal binding protein involved in sirohaem biosynthesis in Bacillus megaterium. Biochem. Soc. Trans. 25: 775.

3. Belfaiza, J.,, A. Martel,, D. Margarita,, and I. Saint Girons. 1998. Direct sulfhydrylation for methionine biosynthesis in Leptospira meyeri. J. Bacteriol. 180: 250– 255.

4. Brush, A.,, and H. Paulus. 1971. The enzymic formation of O-acetylhomoserine in Bacillus subtilis and its regulation by methionine and S-adenosylmethionine. Biochem. Biophys. Res. Commun. 45: 735– 741.

5. Carlsson, J.,, J. T. Larsen,, and M.-B. Edlund. 1993. Peptostreptococcus micros has a uniquely high capacity to form hydrogen sulfide from glutathione. OralMicrobioi. Immunol. 8: 42– 45.

6. Cherest, H.,, D. Thomas,, and Y. Surdin-Kerjan. 1993. Cysteine biosynthesis in Saccharomyces cerevisiae occurs through the transsulfuration pathway which has been built up by enzyme recruitment. J. Bacteriol. 175: 5366– 5374.

7. Cornell, K. A.,, and M. K. Riscoe. 1998. Cloning and expression of Escherichia coli 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase: identification of the pfs gene product. Biochim. Biophys. Acta 1396: 8– 14.

8. Daβler, T.,, T. Maier,, C. Winterhalter,, and A. Bock. 2000. Identification of a major facilitator protein from Escherichia coli involved in efflux of metabolites of the cysteine pathway. Mol. Microbiol. 36: 1101– 1112.

9. Dias, B.,, and B. Weimer. 1998. Conversion of methionine to thiols by Lactococci, Lactobacilli and Brevibacteria. Appl. Environ. Microbiol. 64: 3320– 3326.

10. Ferro, A. J.,, A. Barrett,, and S. K. Shapiro. 1978. 5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose. J. Biol. Chem. 253: 6021– 6025.

11. Fujino, E.,, T. Fujino,, S. Karita,, K. Sakka,, and K. Ohmiya. 1995. Cloning and sequencing of some genes responsible for porphyrin biosyntheis from the anaerobic bacterium Clostridium josui. J. Bacteriol. 177: 5169– 5175.

12. Furfine, E. S.,, and R. H. Abeles. 1988. Intermediates in the conversion of 5′-S-methylthioadenosine to methionine in Klebsiella pneumoniae. J. Biol. Chem. 263: 9598– 9606.

13. Gagnon, Y. R.,, R. Breton,, H. Putzer,, M. Pelchat,, M. Grunberg-Manago,, and J. Lapointe. 1994 . Clustering and co-transcription of the Bacillus subtilis genes encoding the aminoacyl-tRNA synthetases specific for glutamate and for cysteine and the first enzyme for cysteine biosynthesis. J. Biol. Chem. 269: 7473– 7482.

14. Greene, R. C., 1996. Biosynthesis of methionine, p. 542– 560. In F. C. Neidhardt,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik,, W. S. Reznikoff,, M. Riley,, M. Schaechter,, and E. E. Umbarger (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C.

15. Griffith, O. W. 1987. Mammalian sulfur amino acid metabolism: an overview. Methods Enzymol. 143: 366– 376.

16. Grundy, F. J.,, and T. M. Henkin. 1993. tRNA as a positive regulatory of transcription antitermination in B. subtilis. Cell 74: 475– 482.

17. Grundy, F. J.,, and T. M. Henkin. 1998. The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in Gram-positive bacteria. Mol. Microbiol. 30: 737– 749.

18. Grundy, F. J.,, B. Murphy,, J. Collins,, S. Rollins,, and T. M. Henkin. Unpublished results.

19. Heilbronn, J.,, J. Wilson,, and B. J. Berger. 1999. Tyrosine aminotransferase catalyzes the final step of methionine recycling in Klebsiella pneumoniae. J. Bacteriol. 181: 1739– 1747.

20. Henkin, T. M. 1994. tRNA-directed transcription antitermination. Mol. Microbiol. 13: 381– 387.

21. Hill, R. E.,, and I. D. Spenser,. 1996. Biosynthesis of vitamin B6, p. 695– 703. In F. C. Neidhardt,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik,, W. S. Reznikoff,, M. Riley,, M. Schaechter,, and E. E. Umbarger (ed.), Escherichia coli and Salmonella: Celhdar and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C.

22. Johansson, P.,, and L. Hederstedt. 1999. Organization of genes for tetrapyrrole biosynthesis in Gram-positive bacteria. Microbiology 145: 529– 538.

23. Jungermann, K. A.,, W. Schmidt,, F. H. Kirchiawy,, F. H. Rupprecht,, and R. K. Thauer. 1970. Glycine formation via threonine and serine aldolase. Its interrelation with the pyruvate formate lyase pathway of one-carbon unit synthesis in Clostridium Iduyveri. Eur. J. Biochem. 16: 424– 429.

24. Kane, J. F.,, R. L. Goode,, and J. Wainscott. 1975. Multiple mutations in cysA14 mutants of Bacillus subtilis. J. Bacteriol. 121: 204– 211.

25. Kredich, N. M., 1996. Biosynthesis of cysteine, p. 514– 527. In F. C. Neidhardt,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik,, W. S. Reznikoff,, M. Riley,, M. Schaechter,, and E. E. Umbarger (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C.

26. Kunst, F., et al. 1997. The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390: 249– 256.

27. Kyrpides, N. C.,, and C. R. Woese. 1998. Archael translation initiation revisited: the initiation factor 2 and eukaryotic initiation factor 2B α-β-δ families. Proc. Natl. Acad. Sci. USA 95: 3726– 3730.

28. Mansilla, M. C.,, D. Albanesi,, and D. de Mendoza. 2000. Transcriptional control of the sulfur-regulated cysH operon encoding genes involved in L-cysteine biosynthesis in Bacillus subtilis. J. Bacteriol. 182: 5885– 5892.

29. Mansilla, M. C.,, and D. de Mendoza. 1997. L-cysteine biosynthesis in Bacillus subtilis: identification, sequencing, and functional characterization of the gene coding for phosphoadenylylsulfate sulfotransferase. J. Bacteriol. 179: 976– 981.

30. Mansilla, M. C.,, and D. de Mendoza. 2000. The Bacillus subtilis cysP gene encodes a novel sulphate permease related to the inorganic phosphate transporter (Pit) family. Microbiology 146: 815– 821.

31. Matthews, R. G., 1996. One-carbon metabolism, p. 600– 611. In F. C. Neidhardt,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik,, W. S. Reznikoff,, M. Riley,, M. Schaechter,, and E. E. Umbarger (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biobgy, vol. 1. American Society for Microbiology, Washington, D.C.

32. Miczak, A. 1977. Porphyrin and corrinoid mutants of Bacillus subtilis. J. Bacteriol. 131: 379– 381.

33. Neuhierl, B.,, M. Thanbichler,, F. Lottspeich,, and A. Bock. 1999. A family of S-methylmethionine-dependent thiol/selenol methyltransferases. Role in selenium tolerance and evolutionary relation. J. Biol. Chem. 274: 5407– 5414

34.. O'Neill, G. P.,, M.-W. Chen,, and D. Soil. 1989. Delta-aminolevulinic acid biosynthesis in Escherichia coli and Bacillus subtilis involves formation of glutamyl-tRNA. FEMS Microbiol. Lett. 60: 255– 260.

35. Pasternak, C. A.,, R. J. Ellis,, M. C. Jones-Mortimer,, and C. E. Crichton. 1965. The control of sulphate reduction in bacteria. Biochem. J. 96: 270– 275.

36. Paulus, H., 1993. Biosynthesis of the aspartate family of amino acids, p. 237– 267. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtitis and Other Gram-Positive Bacteria: Biochemistry, Physiohgy, and Molecular Genetics. American Society for Microbiology, Washington, D.C.

37. Peakman, T.,, S. Busby,, and J. Cole. 1990. Transcriptional control of the cysG gene of Escherichia coli K-12 during aerobic and anaerobic growth. Eur. J. Biochem. 191: 325– 331.

38. Piggot, P. J. 1975. Characterization of a cym mutant of Bacillus subtilis. J. Gen. Microbiol. 89: 371– 374.

39. Raux, E.,, A. Lanois,, M. J. Warren,, A. Rambach,, and C. Thermes. 1998. Cobalamin (vitamin B12) biosynthesis: identification and characterization of a Bacillus megaterium cobl operon. Biochem. J. 335: 159– 166.

40. Sekowska, A.,, P. Bertin,, and A. Danchin. 1998. Characterization of polyamine synthesis pathway in Bacillus subtilis 168. Mol. Microbiol. 29: 851– 858.

41. Sekowska, A.,, J.-Y. Coppee,, J.-P. Le Caer,, I. Martin-Verstraete,, and A. Danchin. 2000. S-adenosylmethionine decarboxylase of Bacillus subtilis is closely related to archaebacterial counterparts. Mol. Microbiol. 36: 1135– 1147.

42. Sekowska, A.,, and A. Danchin. 1999. Identification of yrrU as the methylthioadenosine nucleosidase gene in Bacillus subtilis. DNA Res. 6: 255– 264.

43. Shimizu, S.,, S. Shiozaki,, T. Ohshiro,, and H. Yamada. 1984. Occurrence of S-adenosylhomocysteine hydrolase in prokaryote cells. Characterization of the enzyme from Alcaligenes faecalis and the role of the enzyme in the activated methyl cycle. Eur. J. Biochem. 141: 385– 392.

44. Soda, K. 1987. Microbial sulfur amino acids: an overview. Methods Enzymol. 143: 453– 459.

45. Stauffer, G. V., 1996. Biosynthesis of serine, glycine, and one-carbon units, p. 506– 513. In F. C. Neidhardt,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik,, W. S. Reznikoff,, M. Riley,, M. Schaechter,, and E. E. Umbarger (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C.

46. Tabita, F. R. Personal communication.

47. Thanbichler, M.,, B. Neuhierl,, and A. Bock. 1999. S-methylmethionine metabolism in Escherichia coli. J. Bacteriol. 181: 662– 665.

48. van der Ploeg, J. R.,, N. J. Cummings,, T. Leisinger,, and I. F. Connerton. 1998. Bacillus subtilis genes for the utilization of sulfur from aliphatic sulfonates. Microbiology. 144: 2555– 2561.

49. van der Ploeg, J. R.,, M. A. Weiss,, E. Sailer,, H. Nashimoto,, N. Saito,, M. A. Kertesz,, and T. Leisinger. 1996. Identification of sulfate starvation regulated genes in Escherichia coli: a gene cluster involved in the utilization of taurine as a sulfur source. J. Bacteriol. 178: 5438– 5446.

50. Vandeyar, M. A.,, and S. A. Zahler. 1986. Chromosomal insertions of Tn917 in Bacillus subtilis. J. Bacteriol. 167: 530– 534.

51. Vermeij, P.,, and M. A. Kertesz. 1999. Pathways of assimilative sulfur metabolism in Pseudomonas putida. J. Bacteriol. 181: 5833– 5837.

52. Wabiko, H.,, K. Ochi,, D. M. Nguyen,, E. R. Allen,, and E. Freese. 1988. Genetic mapping and physiological consequences of metE mutations in Bacillus subtilis. J. Bacteriol. 170: 2705– 2710.

53. Wang, L.-F.,, and R. H. Doi. 1990. Complex character of senS, a novel gene regulating expression of extracellular-protein genes of Bacillus subtilis. J. Bacteriol. 172: 1939– 1947.

54. Weimer, B.,, K. Seefeldt,, and B. Dias. 1999. Sulfur metabolism in bacteria associated with cheese. Antonie Leeuwenhoek 76: 247– 261.

55. Wheldrake, J. F.,, and C. A. Pasternak. 1965. The control of sulphate activation in bacteria. Biochem. J. 96: 276– 280.

56. Wong, L. S.,, M. S. Johnson,, L. B. Sandberg,, and B. L. Taylor. 1995. Amino acid efflux in response to chemotactic and osmotic signals in Bacillus subtilis. J. Bacteriol. 177: 4342– 4349.

57. Yeggy, J. P.,, and D. P. Stahly. 1980. Sporulation and regulation of homoserine dehydrogenase in Bacillus subtilis. Can. J. Microbiol. 26: 1386– 1391.

58. Yocum, R. R.,, J. B. Perkins,, C. L. Howitt,, and J. Pero. 1996. Cloning and characterization of the metE gene encoding S-adenosylmethionine synthetase from Bacillus subtilis. J. Bacteriol. 178: 4604– 4610.

Tables

Synthesis of Serine, Glycine, Cysteine, and Methionine

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TABLE 1

Genes for biosynthesis of serine, glycine, cysteine, and methionine

a Downward arrow indicates direction of transcription of clustered genes. All B. subtilis gene locations and sequence features are based on the SubtiList database (http://genolist.pasteur.fr/SubtiList); information for E. coli was obtained from the Colibri database (http://genolist.pasteur.fr/Colibri), and sequence information for other gram-positive organisms was obtained through The Institute for Genomic Research Microbial Database (http://www.tigr.org/tdb/mdb/mdbinprogress.html).

b Equivalent gene where known in E. coli if the gene name differs from that of B. subtilis.

c ylnD corresponds to the 3′ region of E. coli cysG; ylnF corresponds to the 5' region of E. coli cysG.

d T-box (Thr) in Clostridium difficile.

e This step is catalyzed by homoserine O-succinyltransferase in E. coli.

f S-box gene in Clostridium acetobutylicum.

g T-box (met) in Staphylococcus aureus.

h This enzyme, which bypasses yjcI and yjcJ, is found in Clostridium and Brevibacterium spp. but not in B. subtilis or E. coli.

i The metH form of methionine synthase is found in Clostridium sp. but not in B. subtilis.

j yitJ contains a homocysteine binding domain at its 5′ end, absent in E. coli metF.

k T-box (Met) in C. difficile.

l T-box (Cys) in C. difficile.

m T-box (Met) in Enterococcus faecalis.

n S-box in Bacillus anthacis.

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TABLE 1

Genes for biosynthesis of serine, glycine, cysteine, and methionine

b Equivalent gene where known in E. coli if the gene name differs from that of B. subtilis.

c ylnD corresponds to the 3′ region of E. coli cysG; ylnF corresponds to the 5' region of E. coli cysG.

d T-box (Thr) in Clostridium difficile.

e This step is catalyzed by homoserine O-succinyltransferase in E. coli.

f S-box gene in Clostridium acetobutylicum.

g T-box (met) in Staphylococcus aureus.

h This enzyme, which bypasses yjcI and yjcJ, is found in Clostridium and Brevibacterium spp. but not in B. subtilis or E. coli.

i The metH form of methionine synthase is found in Clostridium sp. but not in B. subtilis.

j yitJ contains a homocysteine binding domain at its 5′ end, absent in E. coli metF.

k T-box (Met) in C. difficile.

l T-box (Cys) in C. difficile.

m T-box (Met) in Enterococcus faecalis.

n S-box in Bacillus anthacis.