Skip to main content
Log in

Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations

  • Original Paper
  • Biotechnology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Clavulanic acid (CA) was produced by Streptomyces clavuligerus in medium containing glycerol and soy meal or soy meal extract. With regard to growth and CA productivity, the microorganism showed significant differences if solid soy meal as such or its extract were applied as the major nitrogen source. If the extract is used, growth and CA production take place simultaneously and in the stationary phase the CA concentration is stagnant or reduces. If soy meal is used, growth is threefold faster and CA is only generated in the stationary phase. In the case of using the soy meal extract, the decrease of the CA concentration is mainly due to decomposition or re-metabolisation of CA in the presence of the microorganism. This conclusion is supported by in vivo and in vitro data on CA decomposition.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aharonowitz Y, Demain AL (1978) Carbon catabolite regulation of cephalosporin production in Streptomyces clavuligerus. Antimicrob Agents Chemother 14: 159–164

    CAS  Google Scholar 

  • Brown AG, Corbett DF, Goodacre J, Harbridge JB, Howarth TT, Ponsford RJ, Stirling I (1984) Clavulanic acid and its derivatives. Structure elucidation of clavulanic acid and the preparation of dihydroclavulanic acid, isoclavulanic acid, esters and related oxidation products. J Chem Soc Perkin Trans I 635–650

  • Doran JL, Leskiw BK, Aippersbach S, Jensen SE (1990) Isolation and characterization of a β-lactamase-inhibitory protein from Streptomyces clavuligerus and cloning and analysis of the corresponding gene. J Bacteriol 172: 4909–4918

    CAS  Google Scholar 

  • Foulstone M, Reading C (1982) Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with HPLC. Antimicrob Agents Chemother 22: 753–762

    CAS  Google Scholar 

  • Hirsch CF, Ensign JC (1976) Nutritionally defined conditions for germination of Streptomyces viridochromogenes spores. J Bacteriol 126: 13–23

    CAS  Google Scholar 

  • Ivanitskaya LP, Bibikova MV, Sharoiko ES, Nikishina VG (1985) Sorbent stimulating effect on biosynthesis of clavulanic acid by Streptomyces clavuligerus ATCC 27604. Antibiot Med Biotekhnol 30: 726–728

    CAS  Google Scholar 

  • Lebrihi A, Germain P, Lefebvre G (1987) Phosphate repression of cephamycin and clavulanic acid production by Streptomyces clavuligerus. Appl Microbiol Biotechnol 26: 130–135

    Article  CAS  Google Scholar 

  • Lebrihi A, Lefebvre G, Germain P (1988) Carbon catabolite regulation of cephamycin C and expandase biosynthesis in Streptomyces clavuligerus. Appl Microbiol Biotechnol 28: 44–51

    CAS  Google Scholar 

  • Martín JF, Demain AL (1980) Control of antibiotic biosynthesis. Microbiol Rev 44: 230–251

    Google Scholar 

  • Mendelovitz S, Aharonowitz Y (1982) Regulation of cephamycin C synthesis, aspartokinase, dihydrodipicolinic acid synthetase and homoserine dehydrogenase by aspartic acid family amino acids in Streptomyces clavuligerus. Antimicrob Agents Chemother 21: 74–84

    CAS  Google Scholar 

  • Reading C, Cole M (1977) Clavulanic acid: a β-lactamase-inhibiting β-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11: 852–857

    CAS  Google Scholar 

  • Romero J, Liras P, Martn JF (1984) Dissociation of cephamycin and clavulanic acid biosynthesis in Streptomyces clavuligerus. Appl Microbiol Biotechnol 20: 318–325

    Article  CAS  Google Scholar 

  • Salowe SP, Krol WJ, Iwata-Reuyl D, Townsend CA (1991) Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction. Biochemistry 30: 2281–2292

    Article  CAS  Google Scholar 

  • Valentine BP, Bailey CR, Doherty A, Morris J, Elson SW, Baggaley KH, Nicholson NH (1993) Evidence that arginine is a later metabolic intermediate than ornithine in the biosynthesis of clavulanic acid by Streptomyces clavuligerus. J Chem Soc Chem Commun 1210–1211

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mayer, A.F., Deckwer, W.D. Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations. Appl Microbiol Biotechnol 45, 41–46 (1996). https://doi.org/10.1007/s002530050646

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002530050646

Keywords

Navigation