Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Repression and inhibition of cephalosporin synthetases in Streptomyces clavuligerus by inorganic phosphate


Cephalosporin production by growing cells of Streptomyces clavuligerus was reduced by 100 mM inorganic phosphate. Resting cell production was repressed by prior growth in high phosphate and inhibited by phosphate. The cell-free activity of desacetoxycephalosporin C synthetase (ring expansion activity) was repressed by prior growth in high phosphate and inhibited by phosphate. Isopenicillin N synthetase (cyclase) was inhibited but not repressed. Penicillin epimerase was neither inhibited nor repressed by phosphate.

This is a preview of subscription content, log in to check access.



dry cell weight


3-(N-morpholino) propane-sulfonic acid


  1. Aharonowitz Y, Demain AL (1977) Influence of inorganic phosphate and organic buffers on cephalosporin production by Streptomyces clavuligerus. Arch Microbiol 115:169–173

  2. Behmer CJ, Demain AL (1983) Further studies on carbon catabolite regulation of β-lactam antibiotic synthesis in Cephalosporium acremonium. Curr Microbiol 8:107–114

  3. Demain AL((1983) Biosynthesis of β-lactam antibiotics. In: Demain AL, Solomon NA (eds) Antibiotics containing the β-lactam structure. Springer, Berlin Heidelberg New York, pp 189–228

  4. Demain AL, Aharonowitz Y, Martin JF (1983) Metabolic control of secondary biosynthetic pathways. In: Vining LC Biochemictry and genetic regulation of commercially important antibiotics. Addison-Wesley, Reading, MA, pp 49–72

  5. Heim J, Shen Y-Q, Wolfe S, Demain AL (1984) Regulation of isopenicillin N synthetase and deacetoxycephalosporin C synthetase by carbon source during the fermentation of Cephalosporium acremonium. Appl Microbiol & Biotechnol 19:232–236

  6. Jensen SE, Westlake DWS, Wolfe S (1982) Cyclization of δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine to penicillins by cell-free extracts of Streptomyces clavuligerus. J Antibiot 35:483–490

  7. Jensen SE, Westlake DWS, Wolfe S (1983) Partial purification and characterization of isopenicillin N epimerase activity from Streptomyces clavuligerus. Can J Microbiol 29:1526–1531

  8. Küenzi MT (1980) Regulation of cephalosporin synthesis in Cephalosporium acremonium by phosphate and glucose. Arch Microbiol 128:78–83

  9. Kupka J, Shen Y-Q, Wolfe S, Demain AL (1983a) Partial purification and properties of the α-ketoglutarate-linked ring-expansion enzyme of β-lactam biosynthesis of Cephalosporium acremonium. FEMS Microbiol Lett 16:1–6

  10. Kupka J, Shen Y-Q, Wolfe S, Demain AL (1983b) Studies on the ring cyclization and ring-expansion enzymes of β-lactam biosynthesis in Cephalosporium acremonium. Can J Microbiol 29:488–496

  11. Lilley G, Clark AE, Lawrence GC (1981) Control of the production of cephamycin C and thienamycin by Streptomyces cattleya NRRL 8057. J Chem Tech Biotechnol 31:127–134

  12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

  13. Martin JF, Demain AL (1976) Control by phosphate of candicidin production. Biochem Biophys Res Commun 71:1103–1109

  14. Taussky HH, Shorr E (1953) A microcolorimetric method for the determination of inorganic phosphorus. J Biol Chem 202:675–685

  15. Vandamme EJ, Demain AL (1976) Nutrition of Bacillus brevis ATCC 9999, the producer of gramicidin S. Antimicrob Agents Chemother 10:267–273

  16. Zanca DM, Martin JF (1983) Carbon catabolite regulation of the conversion of penicillin N into cephalosporin C. J Antibiot 36:700–708

Download references

Author information

Correspondence to Arnold L. Demain.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lübbe, C., Wolfe, S. & Demain, A.L. Repression and inhibition of cephalosporin synthetases in Streptomyces clavuligerus by inorganic phosphate. Arch. Microbiol. 140, 317–320 (1985).

Download citation

Key words

  • Phosphate regulation
  • Cephalosporin synthetases
  • Streptomyces clavuligerus
  • Cephamycin
  • Antibiotic Fermentation