Skip to main content
PMC home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1980 Dec;144(3):869–876. doi: 10.1128/jb.144.3.869-876.1980

Inhibition and repression of homocitrate synthase by lysine in Penicillium chrysogenum.

J M Luengo, G Revilla, M J López, J R Villanueva, J F Martín
PMCID: PMC294747  PMID: 6777369

Abstract

Homocitrate synthase in the first enzyme of the lysine biosynthetic pathway. It is feedback regulated by L-lysine. Lysine decreases the biosynthesis of penicillin (determined by the incorporation of [14C]valine into penicillin) by inhibiting and repressing homocitrate synthase, thereby depriving the cell of alpha-aminoadipic acid, a precursor of penicillin. Lysine feedback inhibited in vivo the biosynthesis and excretion of homocitrate by a lysine auxotroph, L2, blocked in the lysine pathway after homocitrate. Neither penicillin nor 6-aminopenicillanic acid exerted any effect at the homocitrate synthase level. The molecular mechanism of lysine feedback regulation in Penicillium chrysogenum involved both inhibition of homocitrate synthase activity and repression of its synthesis. In vitro studies indicated that L-lysine feedback inhibits and represses homocitrate synthase both in low- and high-penicillin-producing strains. Inhibition of homocitrate synthase activity by lysine was observed in cells in which protein synthesis was arrested with cycloheximide. Maximum homocitrate synthase activity in cultures of P. chrysogenum AS-P-78 was found at 48 h, coinciding with the phase of high rate of penicillin biosynthesis.

Full text

PDF
872

Selected References

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

  1. Bhattacharjee J. K., Strassman M. Accumulation of tricarboxylic acids related to lysine biosynthesis in a yeast mutant. J Biol Chem. 1967 May 25;242(10):2542–2546. [PubMed] [Google Scholar]
  2. DEMAIN A. L. Inhibition of penicillin formation by lysine. Arch Biochem Biophys. 1957 Mar;67(1):244–246. doi: 10.1016/0003-9861(57)90265-5. [DOI] [PubMed] [Google Scholar]
  3. Demain A. L. Biochemistry of penicillin and cephalosporin fermentations. Lloydia. 1974 Jun;37(2):147–167. [PubMed] [Google Scholar]
  4. Demain A. L., Masurekar P. S. Lysine inhibition of in vivo homocitrate synthesis in Penicillium chrysogenum. J Gen Microbiol. 1974 May;82(1):143–151. doi: 10.1099/00221287-82-1-143. [DOI] [PubMed] [Google Scholar]
  5. Friedrich C. G., Demain A. L. Homocitrate synthase as the crucial site of the lysine effect on penicillin biosynthesis. J Antibiot (Tokyo) 1977 Sep;30(9):760–761. doi: 10.7164/antibiotics.30.760. [DOI] [PubMed] [Google Scholar]
  6. Friedrich C. G., Demain A. L. Uptake and metabolism of alpha-aminoadipic acid by Penicillium chrysogenum Wis 54-1255. Arch Microbiol. 1978 Oct 4;119(1):43–47. doi: 10.1007/BF00407926. [DOI] [PubMed] [Google Scholar]
  7. Gaillardin C. M., Poirier L., Heslot H. A kinetic study of homocitrate synthetase activity in the yeast Saccharomycopsis lipolytica. Biochim Biophys Acta. 1976 Feb 13;422(2):390–406. doi: 10.1016/0005-2744(76)90150-9. [DOI] [PubMed] [Google Scholar]
  8. Hogg R. W., Broquist H. P. Homocitrate formation in Neurospora crassa. Relation to lysine biosynthesis. J Biol Chem. 1968 Apr 25;243(8):1839–1845. [PubMed] [Google Scholar]
  9. Konomi T., Herchen S., Baldwin J. E., Yoshida M., Hunt N. A., Demain A. L. Cell-free conversion of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine into an antibiotic with the properties of isopenicillin N in Cephalosporium acremonium. Biochem J. 1979 Nov 15;184(2):427–430. doi: 10.1042/bj1840427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Luengo J. M., Revilla G., Villanueva J. R., Martín J. F. Lysine regulation of penicillin biosynthesis in low-producing and industrial strains of Penicillium chrysogenum. J Gen Microbiol. 1979 Nov;115(1):207–211. doi: 10.1099/00221287-115-1-207. [DOI] [PubMed] [Google Scholar]
  12. Maragoudakis M. E., Holmes H., Strassman M. Control of lysine biosynthesis in yeast by a feedback mechanism. J Bacteriol. 1967 May;93(5):1677–1680. doi: 10.1128/jb.93.5.1677-1680.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masurekar P. S., Demain A. L. Insensitivity of homocitrate synthase in extracts of Penicillium chyrosogenum to feedback inhibition by lysine. Appl Microbiol. 1974 Aug;28(2):265–270. doi: 10.1128/am.28.2.265-270.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Masurekar P. S., Demain A. L. Lysine control of penicillin biosynthesis. Can J Microbiol. 1972 Jul;18(7):1045–1048. doi: 10.1139/m72-162. [DOI] [PubMed] [Google Scholar]
  15. O'Sullivan J., Bleaney R. C., Huddleston J. A., Abraham E. P. Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N. Biochem J. 1979 Nov 15;184(2):421–426. doi: 10.1042/bj1840421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tucci A. F., Ceci L. N. Homocitrate synthase from yeast. Arch Biochem Biophys. 1972 Dec;153(2):742–750. doi: 10.1016/0003-9861(72)90393-1. [DOI] [PubMed] [Google Scholar]
  17. Tucci A. F. Feedback inhibition of lysine biosynthesis in yeast. J Bacteriol. 1969 Aug;99(2):624–625. doi: 10.1128/jb.99.2.624-625.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES