Biocatalysts and Bioreactor Design

Extractive fermentation of clavulanic acid by Streptomyces DAUFPE 3060 using aqueous two-phase system

  1. D. A. Viana Marques1,
  2. A. Pessoa-Júnior1,
  3. J. L. Lima-Filho2,
  4. A. Converti3,*,
  5. P. Perego3,
  6. A. L. F. Porto4

Article first published online: 8 DEC 2010

DOI: 10.1002/btpr.526

Issue

Biotechnology Progress

Biotechnology Progress

Volume 27, Issue 1, pages 95–103, January/February 2011

Additional Information

How to Cite

Viana Marques, D. A., Pessoa-Júnior, A., Lima-Filho, J. L., Converti, A., Perego, P. and Porto, A. L. F. (2011), Extractive fermentation of clavulanic acid by Streptomyces DAUFPE 3060 using aqueous two-phase system. Biotechnol Progress, 27: 95–103. doi: 10.1002/btpr.526

Author Information

  1. 1

    Dept. of Biochemical and Pharmaceutical Technology, University of São Paulo, 05508-000 São Paulo, SP, Brazil

  2. 2

    Dept. of Biochemistry, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil

  3. 3

    Dept. of Chemical and Process Engineering, University of Genoa, 16145 Genoa, Italy

  4. 4

    Dept. of Animal Morphology and Physiology, Federal Rural University of Pernambuco, 52171-900 Dois Irmãos, PE, Brazil

*Dept. of Chemical and Process Engineering, University of Genoa, 16145 Genoa, Italy

Publication History

  1. Issue published online: 10 FEB 2011
  2. Article first published online: 8 DEC 2010
  3. Accepted manuscript online: 8 NOV 2010 08:41AM EST
  4. Manuscript Revised: 8 SEP 2010
  5. Manuscript Received: 29 APR 2010

Funded by

  • Brazilian Research Funding Institutions Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Grant Number: 05/60158-0

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Keywords:

  • clavulanic acid;
  • extractive fermentation;
  • ATPS;
  • integrated process;
  • optimization

Abstract

The influence of four variables, specifically PEG molar mass (400, 1,000, and 8,000 g/mol), concentrations of PEG and phosphate salts (15, 20, and 25% for both), and agitation intensity (110, 150, and 200 rpm), on clavulanic acid (CA) extraction by extractive fermentation with PEG/phosphate salts aqueous two-phase system was investigated in shaken flasks using a 24-1-fractional factorial design. After selection of the two most significant variables (agitation intensity and PEG molar mass), an optimization study conducted according to a 22-central composite design revealed that 25% PEG 8,000 g/mol and phosphate salts at 240 rpm (run 6) were the best conditions for the extractive fermentation, leading to the best results in terms of partition coefficient (k = 8.2), yield of CA in the PEG-rich phase (ηT = 93%) and productivity (P = 5.3 mg/Lh). As a first attempt to make a scale-up of these results, the effectiveness of the extractive fermentation was then checked in a bench-scale bioreactor under conditions as close as possible to the optimum ones determined in flasks. The highest CA concentration obtained in the PEG-rich phase (691 mg/L) was 30% higher than in flasks, thus demonstrating the potential of such a new process, integrating the production and extraction steps, as a promising, low-cost tool to obtain high yields of this and similar products. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2011

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