1887

Abstract

During a 6 h incubation at 26 °C, hydroxylated progesterone predominantly at the 14α site. Further incubation resulted in the production of several 14α-dihydroxyprogesterones and a novel microbial transformation product, 8(9), 14(15)-didehydroprogesterone (pregna-4,8[9], 14[15]-triene-3,20-dione). Azole inhibition indicates that the hydroxylases are cytochromes P-450. Mycelia transformed in the presence of the translation inhibitor cycloheximide failed to hydroxylate progesterone, whereas identical treatment with the transcription inhibitor actinomycin D, or heat-shock for 1 h at 37 °C prior to progesterone transformation, stimulated hydroxylation. 14α-Hydroxylation was stimulated if mycelia were pre-incubated with progesterone, transcription or translation inhibitors. These data are consistent with a model in which cytochrome P-450 steroid hydroxylase mRNA is stored in cells in a dormant form by a labile sequestering protein.

Loading

Article metrics loading...

/content/journal/micro/10.1099/13500872-140-7-1633
1994-07-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/140/7/mic-140-7-1633.html?itemId=/content/journal/micro/10.1099/13500872-140-7-1633&mimeType=html&fmt=ahah

References

  1. Attar R.M., Grotewold E., Taccioli G.E., Aisemberg G.O., Torres H.N., Judewicz N.D. A cvcloheximide-inducible gene of Neurospora crassa belongs to the cytochrome P-450 superfamily. Nucleic Acids Res 1989; 17:7535–7536
    [Google Scholar]
  2. Ballard S.A., Ellis S., W., Kelly S.L., Troke P.F. Ergosterol biosynthesis by a cell-free preparation of Aspergillus fumimtus and its inhibition by azole anti-fungal agents. J Med Vet Mycol 1990; 28:335–344
    [Google Scholar]
  3. Breskvar K., Hudnik-Plevnik T. Inducibility of progesterone hydroxylating enzymes in Rhizopus nigricans. J Steroid Biochem 1978; 9:131–134
    [Google Scholar]
  4. Charney W., Herzog H.L. Microbial Transformation of Steroids: a Handbook 1967 New York: Academic Press;
    [Google Scholar]
  5. Durst F., Benveniste I., Salaun J., Werck-Reichhart D. Function, mechanism and regulation of cytochrome P-450 enzymes in plants. Biochem Soc Trans 1992; 20:353–357
    [Google Scholar]
  6. Grotewold E., Taccioli G.E., Aisemberg G.O., Judewicz N.D. Early response and induced tolerance to cycloheximide in Neurospora crassa. Curr Gen 1989; 15:429–434
    [Google Scholar]
  7. Hamilton J.W., Bement W.J., Sinclair P.R., Sinclair J.F., Alcedo J.A., Wetterhahn K.E. Inhibition of protein synthesis increases the transcription of the phenobarbital-induced CYP2H1 and CYP2H2 genes in chick embryo hepatocytes. Arch Biochem Biophys 1992; 298:98–104
    [Google Scholar]
  8. Hentze M.W. Determinants and regulation of cytoplasmic mRNA stability in eukaryotic cells. Biochim Biophys Acta 1991; 1090:281–292
    [Google Scholar]
  9. Hogg J.A. Steroids, the steroid community, and Upjohn in perspective: a profile of innovation. Steroids 1992; 57:593–616
    [Google Scholar]
  10. Jayanthi C.R., Madyastha P., Madyastha K.M. Microsomal 11a hydroxylation of progesterone in Aspergillus ochraceus: part I: characterisation of the hydroxylase system. Biochem Biophys Rtft Commun 1982; 106:1262–1268
    [Google Scholar]
  11. Kirk D.N., Toms H.C., Douglas C, White K.A., Smith K.E., Latif S., Hubbard R.W.P. A survey of the high-field lH NMR spectra of the steroid hormones, their hydroxylated derivatives,and related compounds. Chem SocPerkin Trans 1990; 2:567–1594
    [Google Scholar]
  12. Loreni F., Franesconi A., Jappelli R., Amaldi F. Analysis of mRNAs under translational control during Xenopus embryo-genesis: isolation of new ribosomal protein clones. Nucleic Acids Res 1992; 20:1859–1863 and references therein
    [Google Scholar]
  13. Lusska A., Wu L., Whitlock J.P. Jr Super induction of CYP1A1 transcription by cycloheximide. J Biol Chem 1992; 267:15146–15151
    [Google Scholar]
  14. Madyastha K., Jayanthi C.R., Madyastha P., Sumathi D. Studies on the microbial 11a hydroxylation of progesterone in Aspergillus ochraceus: characterisation and solubilisation of the hydroxylase system. Can J Biochem Cell Biol 1984; 62:100–107
    [Google Scholar]
  15. Nebert D.W., Nelson D.R., Coon M.J., Estabrook R.W., Feyereisen R., Fuji-Kyriyama Y., Gonzalez F.J., Guengerich F.P., Gunsalus I.C., Johnson E.F., Loper J.C., Sato R., Waterman M.R., Waxman D.J. The P450 super family: update on new sequences, gene mapping and recommended nomenclature. DNA Cell Biol 1991; 10:1–14
    [Google Scholar]
  16. Nemoto N., Sakurai J. Increase of CYP1A1 mRNA and AHH activity by inhibitors of either protein or RNA synthesis in mouse hepatocytes in primary culture. Carcinogenesis 1991; 12:2115–2121
    [Google Scholar]
  17. Porter T.D., Coon M.J. Cytochrome P450. Multiplicity of 1991; isoforms:substrates, and catalytic and regulatory mechanisms. J Biol Chem 266, 13469–13472
    [Google Scholar]
  18. Samanta T.B., Ghosh D.K. Characterisation of progesterone 11a hydroxylase of Aspergillus ochraceus TS: a cytochrome P-450 linked monooxygenase. J Steroid Biochem 1987; 28:327–332
    [Google Scholar]
  19. Sariaslani F.S. Microbial cytochromes P-450 and xeno-biotic metabolism. Adv Appl Microbiol 1991; 36:133–178
    [Google Scholar]
  20. Smith K.E., Latif S., Kirk D.N., White K.A. Microbial transformations of steroids -I. Rare transformations of progesterone by Apiocrea chrysosperma. J Steroid Biochem 1988; 31:83–89
    [Google Scholar]
  21. Smith K.E., Latif S., Kirk D.N. Microbial transformations of steroids -II. Transformations of progesterone, testosterone and androstenedione by Phycomyces blakesleeanus. J Steroid Biochem 1989a; 32:445–451
    [Google Scholar]
  22. Smith K.E., Latif S., Kirk D.N. Microbial transformations of steroids -V Transformations of progesterone by whole cells and extracts of Botryosphaeria obtusa. I Steroid Biochem 1989b; 33:927–934
    [Google Scholar]
  23. Smith K.E., Latif S., Kirk D.N. Microbial transformations of steroids -VII Hydroxylation of progesterone by extracts of Phycomyces blakesleeanus. J Steroid Biochem 1991; 38:249–256
    [Google Scholar]
  24. Smith L.L. Microbiological reactions with steroids. Vol. IV. In Specialist Periodical Reports 1974 Edited by Overton K.H. London: The Chemical Society; Terpenoids and Steroids, pp 394–530
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/13500872-140-7-1633
Loading
/content/journal/micro/10.1099/13500872-140-7-1633
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error