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Effect of cycling dissolved oxygen concentrations on product formation in penicillin fermentations

  • Biotechnology
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European journal of applied microbiology and biotechnology Aims and scope Submit manuscript

Summary

Limitations in mass and momentum transfer coupled with high hydrostatic pressures create significant spatial variations in dissolved gas concentrations in large fermenters. Microorganisms are subjected to fluctuating environmental conditions as they pass through the zones in a stirred vessel or along a closed loop fermenter.

A 7-litre fermenter was modified to simulate the dissolved gas and hydrostatic pressure gradients in large vessels.

The effect of cycling dissolved oxygen tension (DOT) on penicillin production by Penicillium chrysogenum P1 was investigated. The fermentation was affected by evironmental conditions such as medium composition, pH, size of inoculum, stirrer speed and DOT. Inoculum size below 10% (v/v) and stirrer speeds above 850 rpm caused significant reductions in specific prenicillin production rates (qpen). qpen values were measured at different constant DOT levels. Below 30% air saturation qpen decreased sharply and no production was observed at 10%. Penicillin synthesis was impaired irreversibly below 10% DOT. The same profile was observed at higher stirrer speeds and air flow rates indicating that the effect was a physiological one. Oxygen uptake of the culture was affected significantly below 7% DOT, demonstrating that the critical DOT values for penicillin production and oxygen uptake are two distinct parameters. Carrying out the fermentation at one atmosphere over pressure was found to have no effect. When the dissolved oxygen concentration of the culture medium was cycled around the critical DOT for penicillin production, a considerable decrease in the specific penicillin production rate was observed. The effect was reversible but not transient, indicating a shift in cell metabolism.

These results demonstrate the unfavourable effect of fluctuating environmental conditions on culture performance in stirred tanks. They suggest that these effects should be accounted for during strain selection, process development and scale up stages of an industrial process if the productivities in small scale vessels are to be obtained.

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References

  • Anderson RF, Tornqvist EGM (1956) Effect of Oil in Pilot Plant Fermentations for Penicillin Production. J Agr Food Chem 4: 556–559

    Google Scholar 

  • Bayer PV (1981) Acceleration of Growth in Microbiological Processes. Unpublished report, Giovanola Freres SA, Montley, Schweiz

    Google Scholar 

  • Bernard A, Cooney CL (1981) Studies on Oxygen Limitations in the Penicillin Fermentation. Eur Cong Biotechnol

  • Bryant J (1977) The Characterization of Mixing in Fermenters. Adv Biochem Eng 5:101–123

    Google Scholar 

  • Bundgaard H, Ilver K (1972) A New Spectrophotometric Method for the Determination of Penicillins. J Pharm Pharmacol 24: 790–794

    Google Scholar 

  • Burton K (1956) A Study of the Conditions and Mechanism of the Diphenylamine Reaction for the Colorimetric Estimation of Deoxyribonucleic Acid. Biochem J 62:315–323

    Google Scholar 

  • Calam CT (1967) Media for Industrial Fermentations. Process Biochem June: 19–22

  • Calam CT (1976) Starting Investigational and Production Cultures. Process Biochem Apr: 7–12

  • Calam CT, Smith GM (1981) Regulation of the Biochemistry and Morphology of Penicillium chrysogenum in Relation to Initial Growth. FEMS Microbiol Lett 10:231–234

    Google Scholar 

  • Camposano A, Chain EB, Gualandi G (1959) The Effect of Mechanical Agitation on the Production of Kojic Acid in Submerged Culture. Sel Sci Pap Ist Sup Sanita 2:224–240

    Google Scholar 

  • Charles M (1978) Technical Aspects of the Rheological Properties of Microbial Cultures. Adv Biochem Eng 8:1–62

    Google Scholar 

  • Evans JI, Hall MJ (1971) Foams and Antifoams in Fermentation. Process Biochem Apr: 23–26

  • Fewkes RJ (1977) Physical Parameters Govering the Biological Activity of a Non-Newtonian Mycelial Fermentation Broth. PhD Thesis, MIT

  • Giona AR, Marelli L, Toro L, De Santis R (1976a) Kinetic Analysis of Penicillin Production by Semicontinuous Fermenters. Biotechnol Bioeng 18:473–492

    Google Scholar 

  • Giona AR, De Santis R, Marelli L, Toro L (1976b) The Influence of Oxygen Concentration and of Specific Rate of Growth on the Kinetics of Penicillin Production. Biotechnol Bioeng 18: 492–512

    Google Scholar 

  • Gurr E, MacConaill MA (1965) The Rational Use of Dyes in Biology, Leonard Hill Co, London

    Google Scholar 

  • Gürtler H (1980) Unpublished Report

  • Harrigan WF, McCane ME (1966) Laboratory Methods in Microbiology, Academic Press, London

    Google Scholar 

  • Jansen PH, Slott S, Gürtler H (1978) Determination of Mixing Times in Large-Scale Fermenters Using Radioactive Isotopes. Eur Congr Biotechnol I, Part 2, Interlaken, pp 80–82

  • Johnson MJ (1946) Metabolism of Penicillin-Producing Moulds. Ann NY Acad Sci 48:57–66

    Google Scholar 

  • Katinger HWD (1976) Physiological Response of Candida tropicalis Grown on n-Paraffin to Mixing in a Tubular Closed Loop Fermenter. Eur J Appl Microbiol Biotechnol 3:103–114

    Google Scholar 

  • König B, Seewald C, Schügerl K (1981a) Untersuchungen zur Penicillin-Produktion unter verfahrenstechnischen Gesichtspunkten. Chem Ing Technol 53:56–57

    Google Scholar 

  • König B, Seewald C, Schügerl K (1981b) Process Engineering Investigations of Penicillin Production. Eur J Appl Microbiol Biotechnol 12:205–211

    Google Scholar 

  • Kubicek CP, Führer L, Zehentrgruber O, Röhr M (1978) The Operation of Oxidative Mechanisms During Citric Acid Fermentation by Aspergillus niger. Eur Congr Biotechnol I, Part 1, Interlaken, pp 131–134

  • Kubicek, CP, Zehentgruber O, El-Kalak H, Röhr M (1980) Regulation of Citric Acid Production by Oxygen: Effect of Dissolved Oxygen Tension on Adenylate Levels and Respiration in Aspergillus niger. Eur J Appl Microbiol Biotechnol 9:101–115

    Google Scholar 

  • Lengyel ZL, Nyiri L (1965) The Inhibitory Effect of Carbon Dioxide on Penicillin Biosynthesis. Antibiot Adv Res Prod Clin Use Proc Congr Prague: 733–735

  • McIntosh AF, Meyrath J (1965) Size of Inoculum and Nitrogen Metabolism in Aspergillus oryzae. J Gen Microbiol 33:57–62

    Google Scholar 

  • Metz B, Kossen NWF (1977) The Growth of Molds in the Form of Pellets. Biotechnol Bioeng 19:781–799

    Google Scholar 

  • Metz B, Kossen NWF, van Suijdam JC (1979) The Rheology of Mould Suspensions. Adv Biochem Eng 11:103–156

    Google Scholar 

  • Meyrath J, McIntosh AF (1965) Size of Inoculum and Carbon Metabolism in Some Aspergillus Species J Gen Microbiol 33: 47–56

    Google Scholar 

  • Meyrath J, Suchanek G (1972) Inoculation Techniques — Effects due to Quality and Quantity of Inoculum. In: Norris JR, Ribbons DW (eds) Methods in Microbiology, vol 7B. Academic Press, London, pp 159–209

    Google Scholar 

  • Ojha MN, Meyrath J (1967) Self-Stimulation and Self-Inhibition in Penicillium chrysogenum. Pathol Microbiol 30:959–965

    Google Scholar 

  • Pan CH, Hepler L, Elander RP (1975) The Effect of Iron on a High Yielding Industrial Strain of Penicillium chrysogenum and Production Levels of Penicillin G. J Ferment Technol 53:854–861

    Google Scholar 

  • Phillips DH, Johnson MJ (1961) Aeration in Fermentations. J Biochem Microbiol Technol Eng 3:277–309

    Google Scholar 

  • Pickett AM, Bazin MJ, Topiwala HH (1979) Growth and Composition of Escherichia coli Subjected to Square Wave Perturbations in Nutrient Supply: Effect of Varying Frequencies. Biotechnol Bioeng 21:1043–1055

    Google Scholar 

  • Placek J, Ujcova E, Musilkova M, Seichert L, Fencl Z (1981) The Role of Mechanical Shear and Cavitations on the Behaviour of Moulds. Inst Microbiol Czech Akad Sci Prague

  • Rao LK, Mathur DK (1975) Studies on the Production of Bacterial Rennet in a Pilot Plant Fermenter Biotechnol Bioeng 17:1349–1361

    Google Scholar 

  • Rolinson GN (1952) Respiration of Penicillium chrysogenum in Penicillin Fermentations. J Gen Microbiol 6:336–343

    Google Scholar 

  • Rolinson GN, Lumb M (1953) The Effect of Aeration on the Utilization of Respiratory Substrates by Penicillium chrysogenum in Submerged Culture. J Gen Microbiol 8:265–272

    Google Scholar 

  • Ryu DY, Humphrey AE (1972) Reassessment of Oxygen Transfer Rates in Antibiotic Fermentations. J Ferment Technol 50:423–431

    Google Scholar 

  • Smith MG, Calam CT (1980) Variations in Inocula and Their Influence on the Productivity of Antibiotic Fermentations. Biotechnol Lett 2:261–266

    Google Scholar 

  • Squires RW (1972) Regulation of the Penicillin Fermentation by means of a Submerged Oxygen-Sensitive Electrode. Dev Ind Microbiol 13:128–135

    Google Scholar 

  • Steel R (1959) Environmental Control of Antibiotic Synthesis, Some Effects of Agitation on Antibiotic Production in Submerged Fermentation. VIIth Int Bot Congr, Montreal

  • Tanaka H, Ueda K (1975) Kinetics of My celial Growth Accompanied by Leakage of Intracellular Nucleotides Caused by Agitation. J Ferment Technol 53:27–34

    Google Scholar 

  • Vardar F (1981) Effect of Cycling Dissolved Oxygen Concentrations on Product Formation in Penicillin Fermentations. PhD Thesis, University College London

  • Vardar F, Lilly MD (1982) The Measurement of Oxygen Transfer Coefficients on Fermenters by Frequency Response Techniques. Biotechnol Bioeng (in press)

  • Wang DIC, Fewkes RCL (1977) Effect of Operating and Geometric Parameters on the Behaviour of Non-Newtonian, My celial, Antibiotic Fermentations. Dev Ind Microbiol 18:39–56

    Google Scholar 

  • Weinberg ED (1970) Biosynthesis of Secondary Metabolites: Roles of Trace Metals. Adv Microbial Physiol 4:1–44

    Google Scholar 

  • Welles JB, Blanch HW (1976) The Effect of Discontinuous Feeding on Ethanol Production by Saccharomyces cerevisiae. Biotechnol Bioeng 18:129–132

    Google Scholar 

  • Ziegler H, Dunn IJ, Bourne JR (1978) Mass Transfer and Myceliali Growth in a Tubular Loop Fermenter. Eur Congr Biotechnol I, Part 1, Interlaken: 74–77

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Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, University College London, WC1E 7JE, London, UK

    F. Vardar & M. D. Lilly

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  1. F. Vardar
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  2. M. D. Lilly
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Vardar, F., Lilly, M.D. Effect of cycling dissolved oxygen concentrations on product formation in penicillin fermentations. European J. Appl. Microbiol. Biotechnol. 14, 203–211 (1982). https://doi.org/10.1007/BF00498464

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  • DOI: https://doi.org/10.1007/BF00498464

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