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Interactions of cell morphology and transport processes in the lovastatin fermentation

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Abstract

The cholesterol lowering drug, Lovastatin (Mevacor), acts as an inhibitor of HMGCoA reductase, and is produced from an Aspergillus terreus fermentation.

Pilot scale studies were carried out in 800 liter fermenters to determine the effects of cell morphology on the oxygen transport properties of this fermentation. Specifically, parallel fermentations giving (i) filamentous mycelial cells, and (ii) discrete mycelial pellets, were quantitatively characterized in terms of broth viscosity, availability of dissolved oxygen, oxygen uptake rates and the oxygen transfer coefficient under identical operating conditions.

The growth phase of the fermentation, was operated using a cascade control strategy which automatically changed the agitation speed with the goal of maintaining dissolved oxygen at 50% saturation. Subsequently stepwise changes were made in agitation speed and aeration rate to evaluate the response of the mass transfer parameters (DO, OUR, and k L a). The results of these experiments indicate considerable potential advantages to the pellet morphology from the standpoint of oxygen transport processes.

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Abbreviations

DO % sat.:

Dissolved oxygen concentration

k L a h−1 :

Gas-liquid mass transfer coefficient

OUR mmol/dm3h:

Oxygen uptake rate

P/V KW/m3 :

Agitator power per unit volume

V s m/s:

Superficial air velocity

μ app cP:

Apparent viscosity

References

  1. Alberts, A. W.; Chen, J.; Kuron, G.; Hunt, V.; Huff, J.; Hoffman, C.; Rothrock, J.; Lopez, M.; Joshua, H.; Harris, E.; Patchett, A.; Monaghan, R.; Currie, S.; Stapley, E.; Alberts-Schonbert, G.; Hensens, O.; Hirshfield, J.; Hoogsteen, K.; Leisch, J.; Springer, J.: Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme, A reductase and a cholesterol-lowering agent. Proc. Natl. Acad. Sci. 77 (1980) 3957–3961

    Google Scholar 

  2. Buckland, B.; Gbewonyo, K.; Hallada, T.; Kaplan, L.; Masurekar, P.: Production of lovastatin. A inhibitor of cholesterol accumulation in humans. Demain, A. L.; Somkuhi, C. A.; Hunter-Cevera, J. C.; Rossmore, H. W. (Eds.): Novel microbial products for medicine and agriculture, pp 161–169, SIM Publication 1989

  3. Whitaker, A.; Long, P. A.: Fungal pelleting. Process Biochemistry 11 (1973) 27–31

    Google Scholar 

  4. Metz, B.; Kossen, N. W. F.: The growth of molds in the form of pellets — a literature review. Biotech. Bioeng. 19 (1977) 781 -797

    Google Scholar 

  5. Schugerl, K.; Wittier, R.; Lorenz, T.: The use of molds in pellet form. Trends. Biotech. 1 (4) (1983) 120–123

    Google Scholar 

  6. Martin, S. M.; Waters, W. R.: Production of citric acid by submerged fermentation. Ind. Eng. Chem. 44 (1952) 2229–2233

    Google Scholar 

  7. Konig, B.; Schugerl, K.: Strategies for penicillin fermentation in tower-loop reactors. Biotech. Bioeng. 24 (1982) 259–280

    Google Scholar 

  8. Takahashi, J.; Yamada, K. J.: Studies on the effects of some physical conditions on the submerged mold culture. Part III: Relations between the morphological forms of molds and the viscosity of mycelial suspensions. J. Agric. Chem. Soc. Japan 34 (1960) 100–103

    Google Scholar 

  9. Chain, E. B.; Gualandi, G.; Morisi, G.: Aeration studies IV. Aeration condition in 3000 liter fermentations of various micro-organisms. Biotech. Bioeng. 8 (1966) 595

    Google Scholar 

  10. Deindoerfer, F. H.; Gaden, E. L.: Effects of liquid physical properties on oxygen transfer in penicillin fermentation. Appl. Microbiol. 3 (1955) 253–257

    Google Scholar 

  11. Gbewonyo, K.; Wang, D. I. C.: Enhancing gas-liquid mass transfer rates in non-newtonian fermentations by confining mycelial growth to microbeads in a bubble column. Biotech. Bioeng. 25 (1983) 2873–2887

    Google Scholar 

  12. Camici, L.; Sermonti, C.; Chain, E. B.: Observations on penicillium chrysogenum in submerged culture 1. Mycelial growth and autolysis. Bull. WHO 6 (1952) 265

    Google Scholar 

  13. Yano, T.; Kodama, T.; Yamada, K.: Fundamental studies on the aerobic fermentation. Part VII. Oxygen transfer within a mold pellet. Agric. Biol. Chem. 25 (1961) 580

    Google Scholar 

  14. Kobayashi, T.; van Dedem, G.; Moo-Young, M.: Oxygen transfer into mycelial pellets. Biotech. Bioeng. 15 (1973) 27–45

    Google Scholar 

  15. Muira, Y.: Transfer of oxygen and scale-up in submerged aerobic fermentation. In Ghose, T. K.; Fietcher, A.; Blakeborough, N. (Eds): Adv. Biochem. Eng. 4 (1976) p 3

  16. Buckland, B. C.; Brix, T.; Fastert, G.; Gbewonyo, K.; Hunt, G.; Jain, D.: Fermentation exhaust gas analysis using mass spectroscopy. Bio/Technology 3 (1985) 982

    Google Scholar 

  17. Buckland, B. C.; Gbewonyo, K.; DiMasi, D.; Hunt, G.; Westerfield, G.; Nienow, A. W.: Improved performance in viscous mycelial fermentations by agitator retrofitting. Biotech. Bioeng. 31 (1988) 737–742

    Google Scholar 

  18. Taguchi, H.; Imanaka, T.; Teramato, S.; Takatsu, M.; Sato, M.: Scale-up of glucamylase fermentation by Endomyces sp. J. Fermentation Technology 46 (1968) 823–828

    Google Scholar 

  19. Cooper, C. M.; Fernstrom, G. A.; Miller, S. A.: Performance of agitated gas-liquid contactors. Industrial and Engineering Chemistry 36 (1944) 504–509

    Google Scholar 

  20. Ryu, D. Y.; Humphrey, A. E.: A reassessment of oxygen transfer rates in antibiotic fermentations. J. Fermentation Technology 50 (1972) 424–431

    Google Scholar 

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Gbewonyo, K., Hunt, G. & Buckland, B. Interactions of cell morphology and transport processes in the lovastatin fermentation. Bioprocess Eng. 8, 1–7 (1992). https://doi.org/10.1007/BF00369257

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