Skip to main content
SpringerLink
Log in

Macrokinetic model for Gluconobacter oxydans in 2-keto-L-gulonic acid mixed culture

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

A set of kinetic models have been developed for the production of 2-keto-L-gulonic acid from L-sorbose by a mixed culture of Gluconobacter oxydans and Bacillus megaterium. A metabolic pathway is proposed for Gluconobacter oxydans, and a macrokinetic model has been developed for Gluconobacter oxydans, where the balances of some key metabolites, ATP and NADH are taken into account. An unstructured model is proposed for concomitant bacterium Bacillus megaterium. In the macrokinetic model and unstructured model, the mechanism of interaction between Gluconobacter oxydans and Bacillus megaterium is investigated and modeled. The specific substrate uptake rate and the specific growth rate obtained from the macrokinetic model are then coupled into a bioreactor model such that the relationship between the substrate feeding rate and the main state variables, such as the medium volume, the biomass concentrations, the substrate, and the is set up. A closed loop regulator model is introduced to approximate the induction of enzyme pool during lag phase after inoculation. Experimental results demonstrate that the model is able to describe 2-keto-L-gulonic acid fermentation process with reasonable accuracy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Reichstein, T. and A. Grussner (1934) Einergiebige synthesis dev L-ascorbinsaure (C-vitamin). Helv. Chim. Acta. 17: 311–328.

    Article  CAS  Google Scholar 

  2. Huang, H. T. (1962) Preparation of 2-keto-L-gulonic acid. US Patent 3,043,749.

  3. Isono, M., I. Nakanishi, K. Sasajima, K. Motizuki, T. Kanzaki, H. Okazaki, and H. Yoshino (1968) 2-keto-l-gulonic acid fermentation. Part I. Paper chromatography characterization of metabolic products from sorbitol and sorbose by various bacteria. Agric. Biol. Chem. 32: 424–431.

    Article  CAS  Google Scholar 

  4. Makover, S., G. B. Ramsey, F. M. Vane, C. G. Witt, and R. B. Wright (1975) New mechanisms for the biosynthesis and metabolism of 2-keto-L-gulonic acid in bacteria. Biotechnol. Bioeng. 17: 1485–1514.

    Article  CAS  Google Scholar 

  5. Martin, C. K. A. and D. Perlman (1976) Conversion of L-sorbose to L-sorbosone by immobilized cells of Gluconobacter melanogenus IFO 3293. Biotechnol. Bioeng. 18: 217–237.

    Article  CAS  Google Scholar 

  6. Zinsheng, Y. (1981) Studies on production of vitamin C precursor 2-keto-L-gulonic acid from L-sorbose by fermentation. Acta Microbiol Sin. 21: 185–191.

    Google Scholar 

  7. Imai, K., T. Sakane, and I. Nogami (1990) Method for producing 2-keto-L-gulonic acid. US Patent 4,892,823.

  8. Yin, G., Z. Tao, Z. Yan, W. Ning, C. Wang, and S. Wang (1990) Fermentation process. US Patent 4,935,359.

  9. Nogami, I., H. Shirafuji, M. Oka, and T. Yamaguchi (1995) Method for producing 2-keto-L-gulonic acid. US Patent 5,474,924.

  10. Sonoyama, T., B. Kagzyan, S. Yagi, and K. Mitsushima (1987) Biochemical aspects of 2-Keto-L-gluonate accumulation from 2,5-diketo-D-gulonate by Corynebacterium sp. and its mutants. Agri. Biol. Chem. 51: 3039–3047.

    Article  CAS  Google Scholar 

  11. Saito, Y., Y. Ishii, H. Hayashi, K. Yoshikawa, Y. Noguchi, S. Yoshida, S. Soeda, and M. Yoshida (1998) Direct fermentation of 2-keto-L-gulonic acid in recombinant Gluconobacter oxydans. Biotechnol. Bioeng. 58: 309–316.

    Article  CAS  Google Scholar 

  12. Stoddard, S. F., H. J. Liaw, and J. D’Elia (2001) Bacterial strains for the production of 2-keto-L-gulonic acid. US Patent 6,316,231.

  13. Yin, G., W. Lin, C. Qiao, and Q. Ye (2001) Production of vitamin C precursor—2-keto-L-gulonic acid from D-sorbitol by mixed culture of microorganisms. Wei sheng wu xue bao. 41: 709–715.

    CAS  Google Scholar 

  14. Urbance, J. W., B. J. Bratina, S. F. Stoddard, and T. M. Schmidt (2001) Taxonomic characterization of Ketogulonigenium vulgare gen. nov., sp. nov. and Ketogulonigenium robustum sp. nov., which oxidize L-sorbose to 2-keto-L-gulonic acid. Int. J. Syst. Evol. Microbiol. 51: 1059–1070.

    Article  CAS  Google Scholar 

  15. Wei, D. Z., W. K. Yuan, and G. L. Yin (1992) Studies on kinetic model of Vitamin C two-step fermentation process. Chin. J. Biotechnol. 8: 277–282.

    CAS  Google Scholar 

  16. Takagi, Y., T. Sugisawa, and T. Hoshino (2010) Continuous 2-Keto-l-gulonic acid fermentation by mixed culture of Ketogulonicigenium vulgare DSM 4025 and Bacillus megaterium or Xanthomonas maltophilia. Appl. Microbiol. Biotechnol. 86: 469–480.

    Article  CAS  Google Scholar 

  17. Feng, S., Z. Zhang, C. Zhang, and Z. Zhang (2000) Effect of Bacillus megaterium on Gluconobacter oxydans in mixed culture. Ying yong sheng tai xue bao. 11: 119–122.

    CAS  Google Scholar 

  18. Lü, S., J. Wang, J. Yao, and Z. Yu (2003) Study on the effect of mutated Bacillus megaterium in two-stage fermentation of vitamin C. Plasma Sci. Technol. 5: 2011–2016.

    Article  Google Scholar 

  19. Tsukada, Y. and D. Perlman (1972) The fermentation of L-sorbose by Gluconobacter melanogenus. III. Investigation of the metabolic pathway from sorbose to 2-keto-L-gulonic acid. Biotechnol. Bioeng. 14: 1035–1038.

    Article  CAS  Google Scholar 

  20. Kitamura, I. and D. Perlman (1975) Metabolism of L-sorbose by enzymes from Gluconobacter melanogenus IFO 3293. European J. Appl. Microbiol. 2: 1–7.

    Article  CAS  Google Scholar 

  21. Hoshino, T., T. Sugisawa, M. Tazoe, M. Shinjoh, and A. Fujiwara (1990) Metabolic pathway for 2-Keto-L-gulonic acid formation in gluconobacter melanogenus IFO3293. Agri. Biol. Chem. 54: 1211–1218.

    Article  CAS  Google Scholar 

  22. Hancock, R. D. and R. Viola (2002) Biotechnological approaches for L-ascorbic acid production. Trends Biotechnol. 20: 299–305.

    Article  CAS  Google Scholar 

  23. Weenk, G., W. Olijve, and W. Harder (1984) Ketogluconate formation by Gluconobacter species. Appl. Microbiol. Biotechnol. 20: 400–405.

    Article  CAS  Google Scholar 

  24. Shinjoh, M., Y. Setoguchi, T. Hoshino, and A. Fujiwara (1990) L-Sorbosone dissimilation in 2-keto-L-gulonic acid-producing mutant UV10 derived from Gluconobacter melanogenes IFO3293. Agri. Biol. Chem. 54: 2257–2263.

    Article  CAS  Google Scholar 

  25. Xu, A., J. M. Yao, and Z. L. Yu (1998) Improvement of mingle strains in the fermentation of 2-keto-L-gulonic acid—precursor of Vc by ion implantation. Industry Microbiol. 28: 21–24.

    CAS  Google Scholar 

  26. Nakamura, M. (1968) Determination of fructose in the presence of a large excess of glucose, part V. A modified cysteine-carbazole reaction. Agric. Biol. Chem. 32: 701–706.

    CAS  Google Scholar 

  27. Hauge, J. G., T. E. King, and V. H. Cheldelin (1955) Oxidation of dihydroxyacetone via the pentose cycle in Acetobacter suboxydans. J. Biol. Chem. 214: 11–26.

    CAS  Google Scholar 

  28. Stouthamer, A. H. (1959) Oxidative possibilities in the catalase positive Acetobacter species. J. Microbiol. Serol. 25: 241–264.

    CAS  Google Scholar 

  29. De Ley, J. (1961) Comparative carbohydrate metabolism and a proposal for a phylogenetic relationship of the acetic acid bacteria. J. Gen. microbiol. 24: 31–50.

    Article  Google Scholar 

  30. Asai, T. (1968) Acetic acid bacteria. Classification and biological activities. University of Tokyo press, Tokyo, and University park press, Baltimore.

    Google Scholar 

  31. Kitos, P. A., C. H. Wang, B. A. Mohler, T. E. King, and V. H. Cheldelin (1958) Glucose and gluconate dissimilation in Acetobacter oxydans. J. Biol. Chem. 233: 1295–1298.

    CAS  Google Scholar 

  32. Jeremy, M. B., L. T. John, and S. Lubert (2002) Biochemistry. 5th ed., W. H. Freeman and Company, NY, USA.

    Google Scholar 

  33. Lee, H. W. and J. G. Pan (1999) Screening for L-sorbose and Lsorbosone dehydrogenase producing microbes for 2-keto-Lgulonic acid production. J. Ind. Microb. Biotech. 23: 106–111.

    Article  CAS  Google Scholar 

  34. Li, G. C. and Z. Z. Zhang (1997) Fermentation characters of 2-KLG-yielding bacteria and optimal model of mixed culture. J. Microbiol. 17: 1–4.

    Google Scholar 

  35. Lu, S. X., L. N. Zhou, S. Feng, Z. Z. Zhang, Y. K. Lu, and H. Y. An (2001) The role of Bacillus megaterium in two-step vitamin C fermentation. J. Microbiol. 21: 3–8.

    CAS  Google Scholar 

  36. Xu, A., J. Yao, L. Yu, S. Lv, J. Wang, B. Yan, and Z. Yu (2004) Mutation of Gluconobacter oxydans and Bacillus megaterium in a two-step process of L-ascorbic acid manufacture by ion beam. J. Appl. Microbiol. 96: 1317–1323.

    Article  CAS  Google Scholar 

  37. Zhao, S., L. Yao, C. Su, T. Wang, J. Wang, M. Tang, and Z. Yu (2008) Purification and properties of a new L-sorbose dehydrogenase accelerative protein from Bacillus megaterium bred by ion-beam implantation. Plasma Sci. Technol. 10: 398–402.

    Article  CAS  Google Scholar 

  38. Zhang, J., J. Liu, Z. Shi, L. Liu, and J. Chen (2010) Manipulation of B. megaterium growth for efficient 2-KLG production by K. vulgare. Proc. Biochem. 45: 602–606.

    Article  CAS  Google Scholar 

  39. Bellgardt, K. H. (1983) Modellbildung des Wachstums von saccharomyces cerevisiae in Ruehrkesselreaktoren. Ph.D. Dissertation. University of Hannover.

  40. Ren, H. T., J. Q. Yuan, and K. H. Bellgardt (2003) Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance. J. Biotechnol. 106: 53–68.

    Article  CAS  Google Scholar 

  41. Zhou, F., J. X. Bi, A. P. Zeng, and J. Q. Yuan (2006) A macrokinetic and regulator model for myeloma cell culture based on metabolic balance of pathways. Proc. Biochem. 41: 2207–2217.

    Article  CAS  Google Scholar 

  42. Pirt, S. J. (1965) The maintenance energy of bacteria in growing cultures. In proceedings of the royal Society of London Series B: Biol. Sci. 163: 224–331.

    Article  CAS  Google Scholar 

  43. Turner, N. A., E. C. Needs, J. A. Khan, and E. N. Vulfson (2001) A rational approach to improving productivity in recombinant Pichia pastoris fermentation. Biotechnol. Bioeng. 72: 1–11.

    Article  Google Scholar 

  44. Lei, F., M. Rotboll, and S. B. Jorgensen (2001) A biochemically structured model for Saccharomyces cerevisiae. J. Biotechnol. 88: 205–221.

    Article  CAS  Google Scholar 

  45. Bellgardt, K. H., W. Kuhlmann, H. D. Meyer, K. Schuegerl, and M. Thoma (1986) Application of an extended Kalman filter for state estimation of a yeast fermentation. IEE Proceedings D: Control Theory and Applications. 133: 226–234.

    Article  Google Scholar 

  46. Murray, J. D. (1993) Mathematical Biology. Heidelberg: Springer.

    Book  Google Scholar 

  47. Lotka, A. J. (1925) Elements of Physical Biology. Williams and Wilkins.

  48. Volterra, V. (1926) Fluctuations in the abundance of a species considered mathematically. Nature. 118: 558–560.

    Article  Google Scholar 

  49. Luedeking, R. and E. L. Piret (2000) Kinetic study of the lactic acid fermentation. Batch process at controlled pH. Biotechnol. Bioeng. 67: 636–644.

    Article  CAS  Google Scholar 

  50. Votruba, J. (1982) Practical aspects of the mathematical modeling of fermentation processes as a method of description, simulation, identification and optimization. Acta Biotechnol. 2: 119–126.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Automation, and the Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai Jiao Tong University, Shanghai, 200-240, China

    Zhixiong Zhang & Jingqi Yuan

  2. New Drugs Research and Development Center, North China Pharmaceutic Group Corporation, Shijiazhuang Hebei, 050-015, China

    Xinjie Zhu

  3. Hebei Welcome Pharmaceutical Co., Ltd., Shijiazhuang Hebei, 050-031, China

    Ping Xie & Junwei Sun

Authors
  1. Zhixiong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinjie Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junwei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingqi Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jingqi Yuan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Z., Zhu, X., Xie, P. et al. Macrokinetic model for Gluconobacter oxydans in 2-keto-L-gulonic acid mixed culture. Biotechnol Bioproc E 17, 1008–1017 (2012). https://doi.org/10.1007/s12257-011-0400-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-011-0400-4

Keywords

Search

Navigation