Skip to main content
Log in

Influence of feeding conditions on clavulanic acid production in fed-batch cultivation with medium containing glycerol

  • Biotechnological Products and Process Engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

First, the effect of different levels of nitrogen source on clavulanic acid (CA) production was evaluated in batch cultivations utilizing complex culture medium containing glycerol and three different levels of soy protein isolate (SPI). Cellular growth, evaluated in terms of the rheological parameter K, was highest with a SPI concentration of 30 g.L−1 (4.42 g.L−1 N total). However, the highest production of CA (380 mg.L−1) was obtained when an intermediate concentration of 20 g.L−1 of SPI (2.95 g.L−1 total N) was used. To address this, the influences of volumetric flow rate (F) and glycerol concentration in the complex feed medium (CsF) in fed-batch cultivations were investigated. The best experimental condition for CA production was F=0.01 L.h−1 and CsF=120 g.L−1, and under these conditions maximum CA production was practically twice that obtained in the batch cultivation. A single empirical equation was proposed to relate maximum CA production with F and CsF in fed-batch experiments.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Badino AC, Facciotti MCR, Schmidell W (1999) Estimation of the rheology of glucoamylase fermentation broth from the biomass concentration and shear conditions. Biotechnol Tech 13:723–726

    CAS  Google Scholar 

  • Baptista-Neto A, Teodoro JC, Cassiano Filho LCM, Badino AC, Hokka CO (2005) Comparison between continuous and batch processing to produce clavulanic acid by Streptomyces clavuligerus. Braz Arch Biol Technol 48:97–104

    Article  Google Scholar 

  • Butterworth D (1984) Clavulanic acid: properties biosynthesis, and fermentation. In: Vandamme EJ (ed) Biotechnology of industrial antibiotics, vol 22. Marcel Dekker, New York, pp 225–235

    Google Scholar 

  • Chen K, Lin Y, Tsai C, Hsieh C, Houng J (2002) Optimization of glycerol feeding for clavulanic acid production by Streptomyces clavuligerus with glycerol feeding. Biotechnol Lett 24:455–458

    Article  CAS  Google Scholar 

  • Chen K, Lin Y, Tsai C, Hsieh C, Houng J (2003) Enhancement of clavulanic acid production in Streptomyces clavuligerus with ornithine feeding. Enzyme Microb Technol 32:152–156

    Article  Google Scholar 

  • Cruz AJG, Silva AS, Araujo MLGC, Giordano RC, Hokka CO (1999) Modelling and optimization of the cephalosporin C production bioprocess in a fed-batch bioreactor with invert sugar as substrate. Chem Eng Sci 54:3137–3142

    Article  CAS  Google Scholar 

  • Elander RP (2003) Industrial production of β-lactam antibiotics. Appl Microbiol Biotechnol 61:385–392

    Article  CAS  Google Scholar 

  • Essack SY (2001) The development of β-lactam antibiotics in response to the evolution of β-lactamases. Pharm Res 18(10):1391–1399

    Article  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

    Article  CAS  Google Scholar 

  • Ives PR, Bushell ME (1997) Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus. Microbiology 143:633–636

    Article  Google Scholar 

  • Mayer AF, Deckwer WD (1996) Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations. Appl Microbiol Biotechnol 45:41–46

    Article  CAS  Google Scholar 

  • Mendz GL, Hazell SL (1996) The urea cycle of Helicobacter pylori. Microbiology 142:2959–2967

    Article  CAS  Google Scholar 

  • Neves AA, Pereira DA, Vieira LM, Menezes JC (2000) Real time monitoring biomass concentration in Streptomyces clavuligerus cultivations with industrial media using a capacitance probe. J Biotechnol 84:45–52

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Rius N, Demain AL (1997) Regulation of lysine ɛ-aminotransferase by carbon source and lack of control phosphate in Streptomyces clavuligerus. Appl Microbiol Biotechnol 48:735–737

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Rosa JC, Baptista Neto A, Hokka CO, Badino AC (2005) Influence of dissolved oxygen and shear conditions on clavulanic acid production by Streptomyces clavuligerus. Bioprocess Biosyst Eng 27:99–104

    Article  CAS  Google Scholar 

  • Roubos JA, Krabben P, de Laat WTAM, Babuska R, Heijnen JJ (2002) Clavulanic acid degradation in Streptomyces clavuligerus fed-batch cultivations. Biotechnol Prog 18:451–457

    Article  CAS  Google Scholar 

  • Sanders CC, Sanders WE (1979) Emergence of resistance to cefamandole: possible role of cefoxitin-inducible β-lactamases. Antimicrob Agents Chemother 15:792–797

    Article  CAS  Google Scholar 

  • Sebastine IM, Stocks SM, Cox PW, Thomas CR (1999) Characterisation of percentage viability of Streptomyces clavuligerus using image analysis. Biotechnol Tech 13:419–423

    Article  CAS  Google Scholar 

  • Spizek J, Tichy P (1995) Some aspects of overproduction of secondary metabolites. Folia Microbiol 40:43–50

    Article  CAS  Google Scholar 

  • Spratt BG (1994) Resistance of antibiotics mediated by target alterations. Science 264:388–394

    Article  CAS  Google Scholar 

  • Wang Y-H, Yang B, Ren J, Dong M-L, Liang D, Xu A-L (2005) Optimization of medium composition for the production of clavulanic acid by Streptomyces clavuligerus. Process Biochem 40:1161–1166

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge Bunge Alimentos S/A for providing the samples of Samprosoy 90NB and the financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant Proc. 03/11722-5 and PD Scholarship Proc.04/00224-7), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alberto C. Badino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teodoro, J.C., Baptista-Neto, A., Cruz-Hernández, I.L. et al. Influence of feeding conditions on clavulanic acid production in fed-batch cultivation with medium containing glycerol. Appl Microbiol Biotechnol 72, 450–455 (2006). https://doi.org/10.1007/s00253-005-0273-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-005-0273-6

Keywords

Navigation