Skip to main content
Log in

Coupling of microbial kinetics and oxygen transfer for analysis and optimization of gluconic acid production with Aspergillus niger

  • Originals
  • Published:
Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Gluconic acid fermentation has been widely used for the analysis of various aspects of kinetics and gas liquid transfer of oxygen. Most of these studies are, however, restricted to processes with bacteria. Mathematical models for industrially important productions with fungi have not been elaborated.

In the experimental part of this work computer coupled fermentations of gluconic acid production with Aspergillus niger NRRL 3 have been performed. Knowledge of the stoichiometric relationship in the key reaction (glucose oxidase) provides an excellent opportunity for on-line estimation of glucose, biomass and product gluconate from oxygen uptake and carbon dioxide evolution rates.

Starting then from experimental observations on the pH-depending oxygen kinetics of gluconic acid formation and influences of product concentrations on the growth of Aspergillus niger a mathematical framework is developed in which the kinetics of growth and production are coupled with gas liquid oxygen transfer. The model can be successfully applied to simulations of the experimental results of gluconic acid fermentations with cyclic addition of glucose. An important aspect in the coupling of transport and microbial reaction in this model is the incorporation of the influence of sugar and gluconate on the solubility of oxygen and k La via changes of viscosities and molecular diffusivities.

With the development of such a comprehensive model, it appears feasible to investigate the influence of various process conditions (sugar feeding, pressure, optimal pH profiles) and to study their possible impacts on the productivity of the overall process.

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

Abbreviations

a 0,a 1,a 2 :

coefficients in the polynom function for the specific production rate (Eq. (17))

b 0,b 1,b 2 :

coefficients in the polynom function for the specific growth rate (Eq. (19))

c 0,c 1,c 2 :

coefficients in pH = f(t)

c L :

concentration of dissolved oxygen

c *L :

saturation concentration of oxygen

\(D_{O_2 } \) :

molecular diffusivity of oxygen in the fermentation fluid

g :

acceleration due to gravity

K M :

Michaelis-Menten constant in the oxygen kinetics

k La:

volumetric mass transfer coefficient

\(m_{Co_{_2 } } \) :

maintenance coefficient for carbon dioxide

m O :

maintenance coefficient for oxygen

m S :

maintenance coefficient for substrate

m 1,m2 :

coefficients (Eqs. (21), (22))

P :

product concentration

P G :

power input under gassed conditions

P max :

critical gluconate concentration for growth

\(Q_{O_2 } \) :

volumetric oxygen uptake rate

\(Q_{CO_2 } \) :

volumetric carbon dioxide evolution rate

\(q_{O_2 } \) :

specific oxygen uptake rate

S :

substrate concentration

Sc:

Schmidt number

t :

time

t:

time at which pH control is switched off

t * :

final fermentation time

t 1 :

switching time for optimal pH control

T :

time constant in the delay of product formation

u G0 :

superficial gas velocity

V L :

liquid volume

V G :

gas flow rate

X :

biomass concentration

\(Y_{Co_2 } \) :

volume fraction of carbon dioxide in the air

\(Y_{o_2 } \) :

volume fraction of oxygen in the air

YX/O \(Y_{x/co_2 } \) 79-08}:

yield coefficients

Y P/O, Y P/S :

yield coefficients

η :

dynamic viscosity

μ :

specific growth rate

μ max :

maximum specific growth rate

ν P :

specific production rate

ν P,max :

maximum specific production rate

ν :

kinematic viscosity

ϱ :

density of the liquid

α :

at the inlet

ω :

at the outlet

References

  1. Yamane, T.; Shimizu, S. 1984: Fed-batch techniques in microbial processes. In: Fiechter, A. (Ed.): Adv. Biochem. Eng./Biotechnol. 30, 147–194

  2. Wang, N. S.; Stephanopoulos, G. 1984: Computer applications for fermentation processes. CRC Critical Reviews in Biotechnology, vol. 2, Issue 1, 1–103

    Google Scholar 

  3. Parulekar, S. J.; Lim, H. C. 1985: Modelling, optimization and control of semi-batch bioreactors. In: Fiechter, A. (Ed.): Adv. Biochem. Eng./Biotechnol. 32, 207–258

  4. Reuss, M. 1983: Mathematical models for coupled oxygen transfer and microbial kinetics in bioreactors. In: Halme, A. (Ed.): Modelling and control of biochemical processes, pp. 43–55. Oxford, New York, Toronto, Sydney, Paris, Frankfurt: Pergamon Press

    Google Scholar 

  5. Oosterhuis, N. M. G.; Kossen, N. W. F. 1984: Dissolved oxygen concentration profiles in a production-scale bioreactor. Biotechnol. Bioeng. 26, 546–550

    Google Scholar 

  6. Oosterhuis, N. M. G.; Kossen, N. W. F.; Olivier, A. P. C; Schenk, E. S. 1985: Scale down and optimization of the gluconic acid fermentation by Gluconobacter oxydans. Biotechnol. Bioeng. 27, 711–720

    Google Scholar 

  7. Gaden, E. L., Jr. 1959: Fermentation process kinetics. J. Biochem. Microbiol. Technol. Eng. 1, 413–429

    Google Scholar 

  8. Wells, P. A.; Moyer, A. J.; Stubbs, J. J.; Herrick, H. T.; May, O. E. 1937: Gluconic acid production. Effect of pressure, air flow, and agitation on gluconic acid production by submerged mold growth. Industr. Eng. Chem. 29, 653–656

    Google Scholar 

  9. Moyer, A. J.; Wells, P. A.; Stubbs, J. J.; Herrick, H. T.; May, O. E. 1937: Gluconic acid production. Development of inoculum and composition of fermentation solution for gluconic acid production by submerged mold growths under increased air pressure. Industr. Eng. Chem. 29, 777–781

    Google Scholar 

  10. Gastrock, E. A.; Porges, N.; Wells, P. A.; Moyer, A. J. 1938: Gluconic acid production on pilot-plant scale. Effect of variables on production by submerged mold growths. Industr. Eng. Chem. 30, 782–789

    Google Scholar 

  11. Moyer, A. J.; Umberger, A. J.; Stubbs, J. J. 1940: Fermentation of concentrated solutions of glucose to gluconic acid. Industr. Eng. Chem. 32, 1379–1383

    Google Scholar 

  12. Humphrey, A. E.; Reilly, P. J. 1965: Kinetic studies of gluconic acid fermentations. Biotechnol. Bioeng. 7, 229–243

    Google Scholar 

  13. Koga, S.; Burg, C. R.; Humphrey, A. E. 1967: Computer simulation of fermentation systems. Appl. Microbiol. 15, 683–689

    PubMed  Google Scholar 

  14. Hsieh, D. P. H.; Silver, R. S.; Mateles, R. I. 1969: Use of the glucose oxidase system to measure oxygen transfer rates. Biotechnol. Bioeng. 11, 1–18

    PubMed  Google Scholar 

  15. Bull, D. N.; Kempe, L. L. 1979: Kinetics of the conversion of glucose to gluconic acid by Pseudomonas ovalis. Biotechnol. Bioeng. 12, 273–290

    Google Scholar 

  16. Tanner, R. D. 1970: An enzyme kinetic model for describing fermentation processes. Biotechnol. Bioeng. 12, 831–843

    PubMed  Google Scholar 

  17. Ghose, T. K.; Mukhopadhyay, S. N. 1976: Kinetic studies of gluconic acid fermentation in horizontal rotary Fermenter by Pseudomonas ovalis. J. Ferment. Technol. 54, 738–750

    Google Scholar 

  18. Ghose, T. K; Ghosh, P. 1976: Kinetic analysis of gluconic acid production by Pseudomonas ovalis. J. Appl. Chem. Biotechnol. 26, 768–777

    Google Scholar 

  19. Ghosh, P.; Ghose, T. K. 1978: Oxygen transfer in gluconic acid fermentation. J. Ferment. Technol. 56, 139–143

    Google Scholar 

  20. Nyeste, L.; Sevella, B.; Szigeti, L.; Szoke, A.; Hollo, J. 1980: Modelling and off-line optimization of batch gluconic acid fermentation. Europ. J. Appl. Microbiol. Biotechnol. 10, 87–94

    Google Scholar 

  21. Zetelaki, K.; Vas, K. 1968: The role of aeration and agitation in the production of glucose oxidase in submerged culture. Biotechnol. Bioeng. 10, 45–59

    Google Scholar 

  22. Zetelaki, K. 1970: The role of aeration and agitation in the production of glucose oxidase in submerged culture. II. Biotechnol. Bioeng. 12, 379–397

    PubMed  Google Scholar 

  23. Novać, M.; Fencl, Z. 1973: Kinetic analysis of the relationship between batch and continuous cultivation of Aspergillus niger. Biotechnol. Bioeng. Symp. Ser. No. 4, 43–52

    Google Scholar 

  24. Machek, F.; Fencl, Z. 1973: Differentiation of filamentous microorganisms as a basis for understanding of product formation. Biotechnol. Bioeng. Symp. Ser. No. 4, 129–142

    Google Scholar 

  25. Takamatsu, T.; Shioya, S.; Furuya, T. 1981: Mathematical model for gluconic acid fermentation by Aspergillus niger. J. Chem. Tech. Biotechnol. 31, 697–704

    Google Scholar 

  26. Gibson, Q. H; Swoboda, B. E. P.; Massey, V. 1964: Kinetics and mechanism of action of glucose oxidase. J. Biol. Chem. 239, 3927–3934

    PubMed  Google Scholar 

  27. Lockwood, L. B. 1979: Production of organic acids by fermentation. In: Peppler, H. J.; Perlman, D. (Eds.): Microbial Technology I, pp. 355–387. London, New York: Academic Press

    Google Scholar 

  28. Röhr, M.; Kubicek, C. P. 1983: Gluconic Acid. In: Rehm, H.-J.; Reed, G. (Eds.): Biotechnology — A comprehensive Treatise in 8 Volumes, vol. 3 (Ed.: Dellweg, H.) Chapter 3 e, pp. 455–465. Weinheim, Deerfield Beach (Florida), Basel: Vlg. Chemie

    Google Scholar 

  29. Deutsches Patentamt: DE 1817 907 (Ger. Pat): Verfahren zur Herstellung einer wäßrigen Lösung von Gluconsäure und einem wasserlöslichen Gluconat durch submerse Vergärung von Glucose

  30. Lien, O. G., Jr. 1959: Determination of gluconolactone, galactonolactone and their free acids by the hydroxamate method. Ann. Chem. 31, 1363–1366

    Google Scholar 

  31. Lenz, R.; Zoll, G. 1982: Rapid determination of sodium gluconate and glucose in fermentation fluids. In: Molnar, I. (Ed.): Practical Aspects of Modern HPLC, pp. 355–361. Berlin, New York: Walter De Gruyter & Co.

    Google Scholar 

  32. Zabriskie, D. W.; Arminger, W. B.; Humphrey, A. E. 1976: Applications of computers to the indirect measurement of biomass concentration and growth rate by component balancing. In: Jefferis, R. P. (Ed.): Workshop Computer Applications in Fermentation Technology, GBF Monograph Ser. No. 3, pp. 59–72. Weinheim, New York: Vlg. Chemie

    Google Scholar 

  33. Zabriskie, D. W.; Humphrey, A. E. 1978: Real-time estimation of aerobic batch fermentation biomass concentration by component balancing. AIChE J. 24, 138

    Google Scholar 

  34. Reuss, M.; Jefferis, R. P.; Lehmann, J. 1976: Application of an on-line system of coupled computer to fermentation modelling. In: Jefferis, R. P. (Ed.): Workshop Computer Application in Fermentation Technology, GBF Monograph Ser. No. 3, pp. 107–124. Weinheim, New York: Vlg. Chemie

    Google Scholar 

  35. Roels, J. A. 1983: Energetics and kinetics in biotechnology. Amsterdam, New York, Oxford: Elsevier Biomedical Press

    Google Scholar 

  36. Watson, T. G. 1970: Effects of sodium chloride on steadystate growth and metabolism of Saccharomyces cerevisiae. J. Gen. Microbiol. 64, 91–99

    PubMed  Google Scholar 

  37. Halme, A. (Ed.), 1983: Modelling and control of biotechnical processes. Oxford, New York, Toronto, Sydney, Paris, Frankfurt: Pergamon Press

    Google Scholar 

  38. Johnson, A. (Ed.), 1985: Modelling and control of biotechnological processes. 1st IFAC Symp., Noordwijkerhout, The Netherlands, 11–13 Dec. 1985, IFAC Proc. Ser. Oxford, New York, Toronto, Sydney, Frankfurt: Pergamon Press

    Google Scholar 

  39. Blanch, H. W. 1981: Invited review microbial growth kinetics. Chem. Eng. Commun. 8, 181–211

    Article  Google Scholar 

  40. Bentley, R. 1963: Glucose oxidase. In: Boyer, P. D.; Lardy, H.; Myrbäck, K. (Eds.): The Enzymes, vol. 7, pp. 567–586. New York, London: Academic Press

    Google Scholar 

  41. Popović, M.; Niebelschütz, H.; Reuss, M. 1979: Oxygen solubilities in fermentation fluids. Europ. J. Appl. Microbiol. Biotechnol. 8, 1–15

    Google Scholar 

  42. Schumpe, A. 1985: Gas solubilities in biomedia. In: Rehm, H.-J.; Reed, G. (Eds.): Biotechnology — A comprehensive treatise in 8 Volumes, vol. 2 (Ed.: Brauer, H.), Chap. 10, pp. 159–170. Weinheim, Deerfield Beach (Florida), Basel: Vlg. Chemie

    Google Scholar 

  43. Henzler, H.-J. 1982: Verfahrenstechnische Auslegungsgrundlagen für Rührbehälter als Fermenter. Chem.-Ing.-Tech. 54, 461–476

    Google Scholar 

  44. Van't Riet, K. 1979: Review of measuring methods and results in non viscous gas-liquid mass transfer in stirred vessels. Ind. Eng. Chem. Process Des. Dev. 18, 367–375

    Google Scholar 

  45. Niebelschütz, H. 1982: Sauerstoffübergang Gas/Flüssigkeit in gerührten Bioreaktoren. Diss. im Fachgebiet Biotechnologie, TU Berlin

  46. Niebelschütz, H.; Reuss, M. 1984: Measurements of oxygen diffusivities in polysaccharide solutions. In: Third European Congress on Biotechnology, vol.II, pp. II579-II584. Weinheim, Deerfield Beach (Florida), Basel: Vlg. Chemie

    Google Scholar 

  47. Rai, V. R.; Constantinides, A. 1973: Mathematical modelling and optimization of the gluconic acid fermentation. AIChE Symp. Ser. 69, 114

    Google Scholar 

  48. Constantinides, A.; Rai, V. R. 1974: Application of the continuous maximum principle to fermentation processes. Biotechnol. Bioeng. Symp. Ser. No. 4, 663–680

    Google Scholar 

  49. Ray, W. H.; Szekely, J. 1973: Process optimization. New York, London, Sydney, Toronto: John Wiley & Sons

    Google Scholar 

  50. Yoshida, T. Sueki, M.; Taguchi, H.; Kulprecha, S.; Nilubol, N. 1981: Modelling and optimization of steroid transformation in a mixed culture. Eur. J. Appl. Microbiol. Biotechnol. 11, 81–88

    Google Scholar 

  51. Guthke, R.; Knorre, W. A. 1981: Optimal substrate profile for antibiotic fermentations. Biotechnol. Bioeng. 23, 2771–2777

    Google Scholar 

  52. Cheruy, A.; Durand, A. 1979: Optimization of erythromycin biosynthesis by controlling pH and temperature: theoretical aspects and practical applications. Biotechnol. Bioeng. Symp. Ser. No. 9, 303–320

    Google Scholar 

  53. Höcker, H. 1979: Untersuchungen zum Leistungseintrag und Stoffübergang in Rührreaktoren. Diss. Univ. Dortmund

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reuss, M., Fröhlich, S., Kramer, B. et al. Coupling of microbial kinetics and oxygen transfer for analysis and optimization of gluconic acid production with Aspergillus niger. Bioprocess Engineering 1, 79–91 (1986). https://doi.org/10.1007/BF00387499

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00387499

Keywords

Navigation