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. 1972 Aug;111(2):547–556. doi: 10.1128/jb.111.2.547-556.1972

Regulation of Homocysteine Biosynthesis in Salmonella typhimurium1

Michael A Savin a, Martin Flavin a, Clarence Slaughter a
PMCID: PMC251317  PMID: 4559736

Abstract

The regulation of the homocysteine branch of the methionine biosynthetic pathway in Salmonella typhimurium has been reexamined with the aid of a new assay for the first enzyme. The activity of this enzyme is subject to synergistic feedback inhibition by methionine plus S-adenosylmethionine. The synthesis of all three enzymes of the pathway is regulated by noncoordinate repression. The enzymes are derepressed in metJ and metK regulatory mutants, suggesting the existence of regulatory elements common to all three. Experiments with a methionine/vitamin B12 auxotroph (metE) grown in a chemostat on methionine or vitamin B12 suggested that the first enzyme is more sensitive to repression by methionine derived from exogenous than from endogenous sources. metB and metC mutants grown on methionine in the chemostat did not show hypersensitivity to repression by exogenous methionine. Therefore, it appears that the metE chemostat findings are peculiar to the phenotype of this mutant; such evidence suggests a possible role for a functional methyltetrahydrofolate-homocysteine transmethylase in regulating the synthesis of the first enzyme. Thus there appear to be regulatory elements which are common to the repression of all three enzymes, as well as some that are unique to the first enzyme. The nature of the corepressor is not known, but it may be a derivative of S-adenosylmethionine. metJ and metK mutants of Salmonella have a normal capacity for S-adenosylmethionine synthesis but may be blocked in synthesis or utilization of a corepressor derived from it.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cauthen S. E., Foster M. A., Woods D. D. Methionine synthesis by extracts of Salmonella typhimurium. Biochem J. 1966 Feb;98(2):630–635. doi: 10.1042/bj0980630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Childs J. D., Smith D. A. New methionine structural gene in Salmonella typhimurium. J Bacteriol. 1969 Oct;100(1):377–382. doi: 10.1128/jb.100.1.377-382.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DELAVIER-KLUTCHKO C., FLAVIN M. ENZYMATIC SYNTHESIS AND CLEAVAGE OF CYSTATHIONINE IN FUNGI AND BACTERIA. J Biol Chem. 1965 Jun;240:2537–2549. [PubMed] [Google Scholar]
  4. Dawes J., Foster M. A. Vitamin B 12 and methionine synthesis in Escherichia coli. Biochim Biophys Acta. 1971 Jun 22;237(3):455–464. doi: 10.1016/0304-4165(71)90263-7. [DOI] [PubMed] [Google Scholar]
  5. FLAVIN M., DELAVIER-KLUTCHKO C., SLAUGHTER C. SUCCINIC ESTER AND AMIDE OF HOMOSERINE: SOME SPONTANEOUS AND ENZYMATIC REACTIONS. Science. 1964 Jan 3;143(3601):50–52. doi: 10.1126/science.143.3601.50. [DOI] [PubMed] [Google Scholar]
  6. Flavin M., Slaughter C. Enzymatic synthesis of homocysteine or methionine directly from O-succinyl-homoserine. Biochim Biophys Acta. 1967 Mar 15;132(2):400–405. doi: 10.1016/0005-2744(67)90158-1. [DOI] [PubMed] [Google Scholar]
  7. Flavin M., Slaughter C. Synthesis of the succinic ester of homoserine, a new intermediate in the bacterial biosynthesis of methionine. Biochemistry. 1965 Jul;4(7):1370–1375. doi: 10.1021/bi00883a022. [DOI] [PubMed] [Google Scholar]
  8. Greene R. C., Su C. H., Holloway C. T. S-Adenosylmethionine synthetase deficient mutants of Escherichia coli K-12 with impaired control of methionine biosynthesis. Biochem Biophys Res Commun. 1970 Mar 27;38(6):1120–1126. doi: 10.1016/0006-291x(70)90355-4. [DOI] [PubMed] [Google Scholar]
  9. Gross T. S., Rowbury R. J. Methionyl transfer RNA synthetase mutants of Salmonella typhimurium which have normal control of the methionine biosynthetic enzymes. Biochim Biophys Acta. 1969 Jun 17;184(1):233–236. doi: 10.1016/0304-4165(69)90126-3. [DOI] [PubMed] [Google Scholar]
  10. Guggenheim S., Flavin M. Cystathionine gamma-synthase from Salmonella. Beta elimination and replacement reactions and inhibition by O-succinylserine. J Biol Chem. 1969 Jul 10;244(13):3722–3727. [PubMed] [Google Scholar]
  11. Holloway C. T., Greene R. C., Su C. H. Regulation of S-adenosylmethionine synthetase in Escherichia coli. J Bacteriol. 1970 Nov;104(2):734–747. doi: 10.1128/jb.104.2.734-747.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kaplan M. M., Flavin M. Cystathionine gamma-synthetase of Salmonella. Catalytic properties of a new enzyme in bacterial methionine biosynthesis. J Biol Chem. 1966 Oct 10;241(19):4463–4471. [PubMed] [Google Scholar]
  13. Kovach J. S., Berberich M. A., Venetianer P., Goldberger R. F. Repression of the histidine operon: effect of the first enzyme on the kinetics of repression. J Bacteriol. 1969 Mar;97(3):1283–1290. doi: 10.1128/jb.97.3.1283-1290.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kovach J. S., Phang J. M., Ference M., Goldberger R. F. Studies on repression of the histidine operon. II. The role of the first enzyme in control of the histidine system. Proc Natl Acad Sci U S A. 1969 Jun;63(2):481–488. doi: 10.1073/pnas.63.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lawrence D. A. Regulation of the methionine feedback-sensitive enzyme in mutants of Salmonella typhimurium. J Bacteriol. 1972 Jan;109(1):8–11. doi: 10.1128/jb.109.1.8-11.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lawrence D. A., Smith D. A., Rowbury R. J. Regulation of methionine synthesis in Salmonella typhimurium: mutants resistant to inhibition by analogues of methionine. Genetics. 1968 Apr;58(4):473–492. doi: 10.1093/genetics/58.4.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee L. W., Ravel J. M., Shive W. Multimetabolite control of a biosynthetic pathway by sequential metabolites. J Biol Chem. 1966 Nov 25;241(22):5479–5480. [PubMed] [Google Scholar]
  18. Leisinger T., Vogel R. H., Vogel H. J. Repression-dependent alteration of an arginine enzyme in Escherichia coli. Proc Natl Acad Sci U S A. 1969 Oct;64(2):686–692. doi: 10.1073/pnas.64.2.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Milner L., Whitfield C., Weissbach H. Effect of L-methionine and vitamin B 12 on methionine biosynthesis in Escherichia coli. Arch Biochem Biophys. 1969 Sep;133(2):413–419. doi: 10.1016/0003-9861(69)90470-6. [DOI] [PubMed] [Google Scholar]
  20. NOVICK A., SZILARD L. Experiments with the Chemostat on spontaneous mutations of bacteria. Proc Natl Acad Sci U S A. 1950 Dec;36(12):708–719. doi: 10.1073/pnas.36.12.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ROWBURY R. J. SYNTHESIS OF CYSTATHIONINE AND ITS CONTROL IN SALMONELLA TYPHIMURIUM. Nature. 1964 Aug 29;203:977–978. doi: 10.1038/203977a0. [DOI] [PubMed] [Google Scholar]
  22. ROWBURY R. J. THE ACCUMULATION OF O-SUCCINYLHOMOSERINE BY ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM. J Gen Microbiol. 1964 Nov;37:171–180. doi: 10.1099/00221287-37-2-171. [DOI] [PubMed] [Google Scholar]
  23. Rowbury R. J., Lawrence D. A., Smith D. A. Regulation of the methionine-specific aspartokinase and homoserine dehydrogenase of Salmonella typhimurium. J Gen Microbiol. 1968 Dec;54(3):337–342. doi: 10.1099/00221287-54-3-337. [DOI] [PubMed] [Google Scholar]
  24. SERCARZ E. E., GORINI L. DIFFERENT CONTRIBUTION OF EXOGENOUS AND ENDOGENOUS ARGININE TO REPRESSOR FORMATION. J Mol Biol. 1964 Feb;8:254–262. doi: 10.1016/s0022-2836(64)80135-2. [DOI] [PubMed] [Google Scholar]
  25. Schlesinger S. Inhibition of growth of Escherichia coli and of homoserine O-transsuccinylase by alpha-methylmethionine. J Bacteriol. 1967 Aug;94(2):327–332. doi: 10.1128/jb.94.2.327-332.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Selhub J., Savin M. A., Sakami W., Flavin M. Synchronization of converging metabolic pathways: activation of the Cystathionine gamma-synthase of Neurospora crassa by methyltetrahydrofolate. Proc Natl Acad Sci U S A. 1971 Feb;68(2):312–314. doi: 10.1073/pnas.68.2.312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith D. A., Childs J. D. Methionine genes and enzymes of Salmonella typhimurium. Heredity (Edinb) 1966 May;21(2):265–286. doi: 10.1038/hdy.1966.22. [DOI] [PubMed] [Google Scholar]
  28. Smith D. A. S-amino acid metabolism and its regulation in Escherichia coli and Salmonella typhimurium. Adv Genet. 1971;16:141–165. doi: 10.1016/s0065-2660(08)60357-0. [DOI] [PubMed] [Google Scholar]
  29. Su C. H., Greene R. C. Regulation of methionine biosynthesis in Escherichia coli: mapping of the metJ locus and properties of a metJ plus-metJ minus diploid. Proc Natl Acad Sci U S A. 1971 Feb;68(2):367–371. doi: 10.1073/pnas.68.2.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tabor H., Tabor C. W. Formation of 1,4-diaminobutane and of spermidine by an ornithine auxotroph of Escherichia coli grown on limiting ornithine or arginine. J Biol Chem. 1969 May 10;244(9):2286–2292. [PubMed] [Google Scholar]

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