Biotechnology and Bioprocess Engineering

, Volume 8, Issue 5, pp 269–278 | Cite as

Bioprocess strategies and recovery processes in gibberellic acid fermentation

  • Ruchi Shukla
  • Ashok K. Srivastava
  • Subhash Chand


Gibberellic acid (GA3) is a commercially important plant growth hormone, which is gaining much more attention all over the world due to its effective use in agriculture and brewing industry. Industrially it is produced by submerged fermentation technique using Ascomycetous fungusGibberella fujikuroi. Solid state and immobilized cell fermentation techniques had also been developed as an alternative to obtain higher yield of GA3. This review summarizes the problems of GA3 fermentation such as production of co-secondary metabolites along with GA3, substrate inhibition and degradation of GA3 to biologically inert compound gibberellenic acid, which limits the yield of GA3 in the fermentation medium. These problems can be overcome by various bioprocessing strategiese.g. two-stage and fed batch cultivation processes. Further research on bioreactor operation strategies such as continuous and/or extractive fermentation with or without cell recycle/retention system need to be investigated for improvement in yield and productivity. Down stream processing for GA3 isolation is also a challenge and procedures available for the same have been critically evaluated.


fermentation gibberellic acid Gibberella fujikuroi 


  1. [1]
    Jefferys, E. G. (1970) The Gibberellin fermentation.Adv. Appl. Biol. 13: 283–316.Google Scholar
  2. [2]
    TudzYnski, B. (1999) Biosynthesis of gibberellin inGibberella fujikuroi bimolecular aspects.Appl. Microbiol. Biotechnol. 52: 298–310.CrossRefGoogle Scholar
  3. [3]
    Bruckner, B. and D. Blechschmidt (1991) The gibberellins fermentation.Crit. Rev. Biotechnol. 11: 163–192.CrossRefGoogle Scholar
  4. [4]
    Kumar, P. K. R. and B. K. Lonsane (1989) Microbial production of gibberellins: State of the art.Adv. Appl. Microbiol. 34: 29–138.CrossRefGoogle Scholar
  5. [5]
    Thakur, M. S. and K. M. Vyas (1983) Production of plant growth regulator by someFusarium sp.Folia. Microbiol. 28: 124–129.CrossRefGoogle Scholar
  6. [6]
    KerenYi, Z., K. Zeller, L. Hornok, and J. F. Leslie (1999) Molecular standardization of mating tYpe terminologY in theGibberella fujikuroi species complex.Appl. Environ. Microbiol. 65: 9: 4071–4076.Google Scholar
  7. [7]
    Linnemannstons, P., J. Schulte, M. del M. Prado, R. H. Proctor, J. Avalos, and B. TudzYnski (2002) The polyketide synthase genepks4 fromGibberella fujikuroi encodes a key enzyme in the biosynthesis of the red pigment bikaverin,Fung. Genetic. Biol. 37: 134–148.CrossRefGoogle Scholar
  8. [8]
    Kawanabe, Y., H. Yamane, T. Murayama, N. Takahashi, and T. Nakamura (1983) Identification of gibberellin A3 in mycelia ofNeurospora crassa.Agric. Biol. Chem. 47: 1693–1694.Google Scholar
  9. [9]
    Sassa, T., K. Suzuki, and E. Haruki (1989) Isolation and identification of gibberellin A4 and A9 from a fungusPhaeosphaeria sp.Agric. Biol. Chem. 53: 303–304.Google Scholar
  10. [10]
    Rademacher, W. (1994) Gibberellin formation in microorganisms.Plant. Growth. Reg. 15: 303–314.CrossRefGoogle Scholar
  11. [11]
    Mander, L. N. (1992) The chemistry of gibberellins: An overview.Chem. Rev. 92: 573–612.CrossRefGoogle Scholar
  12. [12]
    Yabuta, T., Y. Sumiki, and S. Uno (1939) Biochemical studies on bakanae fungus of rice: IV. The cultural condition for producing gibberellin or fusaric acid.J. Agric. Chem. Soc. Japan 15: 1209.Google Scholar
  13. [13]
    Borrow, A., P. W. Brian, V. E. Chester, P. J. Curtis, H. G. Hemming, C. Henehan, E. G. Jeffreys, P. B. Lloyd, I. S. Nixon, G. L. F. Norris, and M. Radley (1955) Gibberellic acid, a metabolic product of the fungusGibberella fujikuroi: some observations on its production and isolation.J. Sci. Food. Agric 6: 340–348.CrossRefGoogle Scholar
  14. [14]
    Gancheva, V., T. Dimova, K. Kamenov, and M. Foutekova (1984) Biosynthesis of gibberellins: III. Optimization of nutrient medium for biosynthesis of gibberellins upon using mathematical methods for planning the experiment.Acta. Microbiol. Bulg. 14: 80–84.Google Scholar
  15. [15]
    Borrow, A., S. Brown, E. G. Jeffreys, R. H. J. Kessell, E. C. Lloyd, P. B. Lloyd, A. Rothwell, and J. C. Swait (1964) The kinetics of metabolism ofGibberella fujikuroi in stirred culture.Can. J. Microbiol. 10: 407–444.Google Scholar
  16. [16]
    Borrow, A., S. Brown, E. G. Jeffrey, R. H. J. Kessel, E. C. Lloyd, P. B. Lloyd, A. Rothwell, and J. C. Swait (1964) The effect of varied temperature on the kinetics of metabolism ofGibberella fujikuroi in stirred culture.Can. J. Microbiol. 10: 445–466.CrossRefGoogle Scholar
  17. [17]
    Bruckner, B. and D. Blechschmidt (1991) Nitrogen regulation of gibberellin biosynthesis inGibberella fujikuroi.Appl. Microbiol. Biotechnol. 35: 646–650.CrossRefGoogle Scholar
  18. [18]
    Silva E. M. E., L. Dendooven, J. A. U. Reynell, A. I. M. Ramirez, G. G. Alatorre, M. M. De la Torre (1999) Morphological development and gibberellin production by different strains ofGibberella fujikuroi in shake flasks and bioreactor.World J. Microbiol. Biotechnol. 15: 753–755.CrossRefGoogle Scholar
  19. [19]
    Sanchez-Marroquin, A. (1963) Microbiological production of gibberellic acid in glucose medium.Appl. Microbiol. 11: 523–528.Google Scholar
  20. [20]
    Darken, M. A., A. L. Jensen, and P. Shu (1959) Production of gibberellic acid by fermentation.Appl. Microbiol. 7: 301–303.Google Scholar
  21. [21]
    Fuska, J., I. Kuhr, M. Podojil, and V. Sevcik (1961) The influence of the nitrogen source on the production of gibberellic acid in submerged cultivation ofGibberella fujikuroi.Folia. Microbiol. 6: 18–21.CrossRefGoogle Scholar
  22. [22]
    Podojil, M., and A. Ricicova (1964) Influence of the soyameal fractions on gibberellic acid and gibberellin A production in submerged cultivation ofG. fujikuroi.Folia. Microbiol. 10: 55–59.CrossRefGoogle Scholar
  23. [23]
    Munoz, G. A. and E. Agosin (1993) Glutamine involvement in nitrogen control of gibberellic acid production inGibberella fujikuroi.Appl. Environ. Microbiol. 59: 12: 4317–4322.Google Scholar
  24. [24]
    Sanchez-Fernandez, R., J. Avalos, and E. Cerda-Olmedo (1997) Inhibition of gibberellin biosynthesis by nitrate inGibberella fujikuroi.FEBS Lett. 413: 35–39.CrossRefGoogle Scholar
  25. [25]
    Bruckner, B. (1992) Regulation of gibberellin formation by the fungusGibberella fujikuroi.Ciba Foundation Symp. 171: 129–137.Google Scholar
  26. [26]
    Gancheva, V. and T. Dimova (1991) Influence of the carbon source on the biosynthesis of gibberellins.Acta. Microbiol. Bulg. 27: 30–34.Google Scholar
  27. [27]
    Gonzalez, P. C., G. Delgado, M. Antigua, J. Rodriguez, P. Larralde, G. Viniegra, L. Pozo, and M. del C. Perez (1994) Some aspects ofGibberella fujikuroi culture concerning gibberellic acid production.Adv. Bioprocess. Eng. 425–430.Google Scholar
  28. [28]
    Hommel, R., K. Nitzsche, G. Basset, S. Schubert, H. J. Huehn, K. H. Schurig, H. Haeckert, B. Geyer, K. Jasche, and E. Schikowsk (1989) Manufacture of gibberellic acid by growth ofFusarium moniliforme on hydrophobic carbon sources.Patent No. DD 267,057.Google Scholar
  29. [29]
    Maddox, I. S. and S. H. Richert (1977) Production of gibberellic acid using a dairy waste as the basal medium.Appl. Environ. Microbiol. 33: 201–202.Google Scholar
  30. [30]
    Gohlwar, C. S., R. P. Sethi, S. S. Marwaha, and V. K. Seghal (1984) Gibberellic acid biosynthesis from whey and simulation of cultural parameters.Enzyme Microb. Technol. 6: 312–316.CrossRefGoogle Scholar
  31. [31]
    Sastry, K. S. M., P. Singh, M. V. V. S. Rao, and C. V. S. Subrahmanyam (1988) Possibility of utilizing industrial residues in gibberellic acid fermentation.Ind. J. Exp. Biol. 26: 851–853.Google Scholar
  32. [32]
    Cihangir, N. and N. Aksoz (1996) Production of gibberellic acid byAspergillus niger using some food industry wastes.Acta. Microbiol. Pol. 45: 291–297.Google Scholar
  33. [33]
    Pastrana, L. M., M. P. Gonzalez, and M. A. Murado (1993) Production of gibberellic acid from mussel processing wastes in submerged batch culture.Bioresource. Technol. 45: 213–221.CrossRefGoogle Scholar
  34. [34]
    Pastrana, L. M., M. P. Gonzalez, A. Torrado, and M. A. Murado (1995) A fed batch culture model for improved production of gibberellic acid from waste medium.Biotechnol. Lett. 17: 263–268.CrossRefGoogle Scholar
  35. [35]
    Holme, T. and B. Zacharias (1965) Gibberellic acid fermentation in continuous culture.Biotechnol. Bioeng. 7: 405–415.CrossRefGoogle Scholar
  36. [36]
    Bu’ Lock, J. D., R. Detroy, Z. Hostalek, and A. Muninal-Shakardu (1974) Regulation of secondary biosynthesis inGibberella fujikuroi.Trans. Br. Mycol. Soc. 62: 377–389.CrossRefGoogle Scholar
  37. [37]
    Gallazzo, J. L. and M. D. Lee (2001) Production of high titers of gibberellins GA4 and GA7 byGibberella fujikuroi strain LTB-1027. Patent No. US 6,287,800.Google Scholar
  38. [38]
    Yan, F. and J. Lin (1999)Gibberella fujikuroi strain used for industrial fermentation production of gibberellins A4 and A7.Patent No. CN 1,222,575.Google Scholar
  39. [39]
    Birch, A. J., I. S. Nixon, and J. H. Grove (1960) Improved process for the manufacture of gibberellic acid.Patent No. GB 844341.Google Scholar
  40. [40]
    Tachibana, A., M. Kubota, and M. Azuma (1994) Gibberellins manufacture withGibberella froment-Kaurene.Patent No. JP 06 90,775.Google Scholar
  41. [41]
    Kumar, P. K. R. and B. K. Lonsane (1987) Potential of fed batch culture in solid-state fermentation for production of gibberellic acid.Biotechnol. Lett. 9: 179–182.CrossRefGoogle Scholar
  42. [42]
    Hesseltine, C. W. (1972) Solid-state fermentation.Biotechnol. Bioeng. 14: 517–532.CrossRefGoogle Scholar
  43. [43]
    Robinson, T., D. Singh, and P. Nigam (2001) Solid-state fermentation a promising microbial technology for secondary metabolite production.Appl. Microbiol. Biotechnol. 55: 284–289.CrossRefGoogle Scholar
  44. [44]
    Kumar, P. K. R. and B. K. Lonsane (1987) Gibberellic acid by solid-state fermentation: Consistent and improved yields.Biotechnol. Bioeng. 30: 267–271.CrossRefGoogle Scholar
  45. [45]
    Kumar, P. K. R. and B. K. Lonsane (1990) SSF: Physical and nutritional factors influencing gibberellic acid production.Appl. Microbiol. Biotechnol. 34: 145–148.CrossRefGoogle Scholar
  46. [46]
    Soccol, C. R., C. M. M. Machado, and O. de Heleno (2001) Production of gibberellic acid by solid state fermentation of a mixed substratePatent No. BR 2000,00,525.Google Scholar
  47. [47]
    Prema, P., M. S. Thakur, S. G. Prapulla, S. V. Ramakrishna, and B. K. Lonsane (1988) Production of gibberellic acid by solid state fermentation: Potential and feasibility.Ind. J. Microbiol. 28: 78–81.Google Scholar
  48. [48]
    Kumar, P. K. R. and B. K. Lonsane (1988) Batch and fed batch solid-state fermentation: kinetics of cell growth, hydrolytic enzymes production and gibberellic acid production.Proc. Biochem. 23: 43–47.Google Scholar
  49. [49]
    Oian, X. M., J. C. du Preez, and S. G. Killan (1994) Ractors affecting gibberellic acid production byF. moniliforme in solid-state cultivation on starch.World. J. Microbiol. Biotechnol. 10: 93–99.CrossRefGoogle Scholar
  50. [50]
    Barrios-Gonzalez, J., A. Tomasini, and C. Fajardo (1997) Gibberellic acid production using different solid state fermentation systems.World. J. Microbiol. Biotechnol. 13: 203–206.CrossRefGoogle Scholar
  51. [51]
    Gelmi, C., R. Perez-Correa, and E. Agosin (2001) Modelling ofG. fujikuroi growth and gibberellic acid production in solid state fermentation.Proc. Biochem. (in press).Google Scholar
  52. [52]
    Bandelier, S., R. Renaud, and A. Durand (1997) Production of gibberellic acid by fed batch solid state fermentation; in an aseptic pilot scale reactor.Proc. Biochem. 32: 141–145.CrossRefGoogle Scholar
  53. [53]
    Agosin, E., M. Maureira, V. Biffani, and F. Perez (1997) Production of gibberellins by solid substrate cultivation ofGibberella fujikuroi. pp. 355–366 In: S. Roussos, B. K. Lonsane, M. Raimbault, and G. Viniegra-Gonzalez, (eds.).Advances in Solid-state Fermentation. Kluwer, Dordrecht, Netherlands.Google Scholar
  54. [54]
    Gelmi, C., R. Perez-Correa, M. Gonzalez, and E. Agosin (2000) Solid substrate cultivation ofGibberella fujikuroi on an inert support.Proc. Biochem. 35: 1227–1233.CrossRefGoogle Scholar
  55. [55]
    Kumar, P. K. R., and B. K. Lonsane (1988) Immobilized growing cells ofGibberella fujikuroi P3 for production of gibberellic acid and pigment in batch and semi continuous culture.Appl. Microbiol. Biotechnol. 28: 537–542.CrossRefGoogle Scholar
  56. [56]
    Silva, E. M. E., L. Dendooven, P. M. Ignacio, R. Magana, S. Parra, and M. De La Torre (2000) Optimization of gibberellic acid production by immobilizedGibberella fujikuroi mycelium in fluidized bioreactors.J. Biotechnol. 76: 147–155.CrossRefGoogle Scholar
  57. [57]
    Nava-Saucedo, J. E., J. N. Barbotin, and D. Thomas (1989) Physiological and morphological modification in immobilizedGibberella fujikuroi mycelia.Appl. Environ. Microbiol. 55: 2377–2384.Google Scholar
  58. [58]
    Nava-Saucedo, J. E., J. N. Barbotin, and D. Thomas (1989) Continuous production of gibberellic acid in a fixed bed reactor by immobilized mycelia ofGibberella fujikuroi in calcium alginate beads.Appl. Microbiol. Biotechnol. 30: 226–233.Google Scholar
  59. [59]
    Kahlon, S. S. and S. Malhotra (1986) Production of gibberellic acid by fungal mycelium immobilized in sodium alginate.Enzyme. Microb. Technol. 8: 613–616.CrossRefGoogle Scholar
  60. [60]
    Jones, J., and R. P. Pharis (1987) Production of gibberellins and bikaverin by cells ofGibberella fujikuroi immobilized in carrageenan.J. Ferment. Technol. 65: 717–722.CrossRefGoogle Scholar
  61. [61]
    Lu, Z., Z. C. Xie, and M. Kumakura (1995) Production of gibberellic acid inGibberella fujikuroi adhered on to polymeric fibrous carrier.Proc. Biochem. 30: 661–665.CrossRefGoogle Scholar
  62. [62]
    Lu, Z., Z. C. Xie, and M. Kumakura (1995) Adhesion ofGibberella fujikuroi cells on surfaces of carriers by radiation polymerization.Radiat. Phys. Chem. 46: 389–393.CrossRefGoogle Scholar
  63. [63]
    Tudzynski, B., P. Hedden, E. Carrera, and P. Gaskin (2001) The P450-4 gene ofGibberella fujikuroi encodesent-Kaurene oxidase in the gibberellin biosynthesis pathway.Appl. Environ. Microbiol. 67: 3514–3522.CrossRefGoogle Scholar
  64. [64]
    Rojas, M. C., P. Hedden, P. Gaskin, and B. Tudzynski (2001) TheP450-1 gene ofGibberella fujikuroi encodes a multifunctional enzyme in gibberellin biosynthesis.Proc. Natl. Acad. Sci. USA 98: 5838–5843.CrossRefGoogle Scholar
  65. [65]
    Tudzynski, B., M. C. Rojas, P. Gaskin, and P. Hedden (2002) The gibberellin 20-oxidase ofGibberella fujikuroi is a multifunctional monooxygenase.J. Biol. Chem. 277: 21246–21253.CrossRefGoogle Scholar
  66. [66]
    Woitek, S., S. S. Unkles, J. R. Kinghorn, and B. Tudzynski (1997) 3-Hydroxy-3-methylglutaryl-CoA reductase gene ofGibberella fujikuroi: Isolation and characterization.Curr. Genet. 31: 38–47.CrossRefGoogle Scholar
  67. [67]
    Homann, V., K. Mende, C. Arntz, V. Ilardi, G. Macino, G. Morelli, G. Bose, and B. Tudzynski (1996) The isoprenoid pathway: Cloning and characterization of fungalFPPS genes.Curr. Genet. 30: 232–239.CrossRefGoogle Scholar
  68. [68]
    Mende, K., V. Homann, and B. Tudzynski (1997) The geranyl geranyl diphosphate synthase gene ofGibberella fujikuroi: Isolation and expression.Mol. Gen. Genetics. 255: 96–105.CrossRefGoogle Scholar
  69. [69]
    Tudzynski, B., and K. Holter (1998) The gibberellin biosynthetic pathway inGibberella fujikuroi: Evidence for a gene cluster.Fungal Genetic. Biol. 25: 157–170.CrossRefGoogle Scholar
  70. [70]
    Graebe, J. E. (1987) Gibberellin biosynthesis and control.Ann. Rev. Plant. Physiol. 38: 419–465.CrossRefGoogle Scholar
  71. [71]
    Hedden, P. and Y. Kamiya (1997) Gibberellin biosynthesis: Enzymes, genes and their regulation.Ann. Rev. Plant. Physiol. 48: 431–460.CrossRefGoogle Scholar
  72. [72]
    Urrutia, O., P. Hedden, and M. C. Royan (2001) Monooxygenase involved in GA12 and GA14 synthesis inGibberella fujikuroi.Phytochemistry 56: 505–511.CrossRefGoogle Scholar
  73. [73]
    Bearder, J. R., J. Mac Millan, M. Wels, M. B. Chaffey, and B. O. Phinney (1974) Position of the metabolic block for gibberellin biosynthesis in mutant B1-41 a ofGibberella fujikuroi.Phytochemistry 13: 911–917.CrossRefGoogle Scholar
  74. [74]
    Giordano, W., J. Avalos, E. Cerda-Olmedo, and C. E. Domenech (1999) Nitrogen availability and production of bikaverin and gibberellins inGibberella fujikuroi.FEMS Microbiol. Lett. 173: 389–393.CrossRefGoogle Scholar
  75. [75]
    Garbayo, J., C. Vilchez, J. E. Nava-Saucedo, and J. N. Barbotin (2003) Nitrogen, carbon and light mediated regulation studies of carotenoid biosynthesis in immobilized mycelia ofGibberella fujikuroi.Enzyme. Microb. Technol. 33: 629–634.CrossRefGoogle Scholar
  76. [76]
    Giordano, W., and C. E. Domenech (1999) Aeration affects acetate destination inGibberella fujikuroi.FEMS Microbiol. Lett. 180: 111–116.CrossRefGoogle Scholar
  77. [77]
    Roisin, C., C. Bienaime, J. E. Nava Saucedo, and J. N. Barbotin (1996) Influence of the microenvironment on immobilizedGibberella fujikuroi.Prog. Biotechnol. 11: 189–195.CrossRefGoogle Scholar
  78. [78]
    Roisin, C., J. E. Nava Saucedo, and J. N. Barbotin (1996) Diversified shunt to the production of different proportions of secondary metabolites (polyketides and terpenes) induced by varying immobilization constraints onGibberella fujikuroi.Ann. N. Y. Acad. Sci. 782: 61–69.CrossRefGoogle Scholar
  79. [79]
    Gerzon, K., H. L. Bird, and D. O. Woolf (1957) Gibberellenic acid a by-product of gibberellic acid fermentation.Experientia 13: 487–489.CrossRefGoogle Scholar
  80. [80]
    Perez, J. F., A. Vecchiola, M. Pinto, and E. Agosin (1996) Gibberellic acid decomposition and its loss of biological activity in aqueous solutions.Phytochemistry 41: 675–679.CrossRefGoogle Scholar
  81. [81]
    Hollmann, D., S. Geipel, J. Switalski, and U. Onken (1995) Extractive fermentation of gibberellic acid byGibberella fujikuroi.J. Ferment. Bioeng. 79: 594–600.CrossRefGoogle Scholar
  82. [82]
    Dockerill, B. and J. R. Hanson (1981) The effect of exogenous gibberellic acid on gibberellin biosynthesis byGibberella fujikuroi.Phytochemistry. 20: 2679–2681.CrossRefGoogle Scholar
  83. [83]
    Goswami, V. and A. K. Srivastava (2001) Propionic acid production in anin situ cell retention bioreactor.Appl. Microbiol. Biotechnol. 56: 676–680.CrossRefGoogle Scholar
  84. [84]
    Laplace, J. M., J. P. Delgenes, R. Moletta, and J. M. Navarro (1993) Ethanol production from glucose and xylose by separated and coculture processes using high cell density system.Proc. Biochem. 28: 519–525.CrossRefGoogle Scholar
  85. [85]
    Mulchandani, A. and B. Volesky (1994) Production of acetone-butanol ethanol byClostridium acetobutylicum using a spin filter perfusion bioreactor.J. Biotechnol. 34: 51–60.CrossRefGoogle Scholar
  86. [86]
    Melzoch, K., J. Votruba, V. Habova, and M. Rychtera (1997) Lactic acid production in a cell retention continuous culture using lignocellulosic hydrolyzate as a substrate.J. Biotechnol. 56: 25–31.CrossRefGoogle Scholar
  87. [87]
    Freeman, A., J. M. Woodley, and M. D. Lilly (1993)In situ product removal as a tool for bioprocessing.Biotechnol. 11: 1007–1012.CrossRefGoogle Scholar
  88. [88]
    Zijlstra, G. M., C. D. de Gooijer, and J. Tramper (1998) Extractive bioconversions in aqueous two-phase systems.Curr. Opin. Biotechnol. 9: 171–176.CrossRefGoogle Scholar
  89. [89]
    Muge, K., B. Emine, A. Selma, and M. Ulku (2002) Investigation of extractive citric acid fermentation using response surface methodology.Proc. Biochem. 37: 759–767.CrossRefGoogle Scholar
  90. [90]
    Gu, Z., B. A. Glatz, and C. E. Glatz (1998) Propionic acid production by extractive fermentation: I Solvent considerations.Biotechnol. Bioeng. 57(4): 454–461.CrossRefGoogle Scholar
  91. [91]
    Zigova, J., E. Sturdik, D. Vandak, and S. Schlosser (1999) Butyric acid production byClostridium butyricum with integrated extraction and pertraction.Proc. Biochem. 34: 835–843.CrossRefGoogle Scholar
  92. [92]
    Matsumoto, M., T. Takagi, and K. Kondo (1998) Separation of lactic acid using polymeric membrane containing a mobile carrier.J. Ferment. Bioeng. 85: 483–487.CrossRefGoogle Scholar
  93. [93]
    Sinha, J., P. K. Dey, and T. Panda (2000) Aqueous two phase: the system of choice for extractive fermentation.Appl. Microbiol. Biotechnol. 54: 476–486.CrossRefGoogle Scholar
  94. [94]
    Kuhn, I. (1980) Alcoholic fermentation in an aqueous two-phase system.Biotechnol. Bioeng. 22: 2393–2398.CrossRefGoogle Scholar
  95. [95]
    Mattiasson, B., M. Suominen, E. Andersson, L. Haggstrom, P. A. Albertsson, and B. Hahn-Hagerdal (1982) Solvent production byClostridium acetobutylicum in aqueous two phase system. pp. 153–155. In: I. Chibata, S. Fukui and L. B. Wingard (eds.),Enzyme Engineering. Vol. 6, Plenum, NY, USA.Google Scholar
  96. [96]
    Kwon, Y. J., R. Kaul, and B. Mattiasson (1996) Extractive lactic acid fermentation in poly (ethyleneimine)-based aqueous two-phase system.Biotechnol. Bioeng. 50: 280–290.CrossRefGoogle Scholar
  97. [97]
    Gupta, V., S. Nath, and S. Chand (2002) Electrostatic interactions, phase separation behaviour and partitioning of proteins in polyelectrolyte based aqueous two-phase systems.Ind. J. Biotechnol. 1: 87–95.Google Scholar
  98. [98]
    Borrow, A., E. G. Jeffery, and I. S. Nixon (1959) Process of producing GA3 by two stage cultivation ofGibberella fujikuroi. Patent No. US 2, 906670.Google Scholar
  99. [99]
    Timothy, D. L. and S. D. Bruce (2000) Xylitol production from corn fibre hydrolysates by a two-stage fermentation process.Proc. Biochem. 35: 765–769.CrossRefGoogle Scholar
  100. [100]
    De Carvalho Lima, K. G., C. M. Takahashi, and F. Alterthum (2002) Ethanol production from corn cob hydrolysates byEscherichia coli: KO11.J. Ind. Microbiol. Biotechnol. 29: 124–128.CrossRefGoogle Scholar
  101. [101]
    Fang, Q. H. and J. J. Zhong (2002) Two-stage culture process for improved production of ganoderic acid by liquid fermentation of higher fungusGanoderma lucidum.Biotechnol. Prog. 18: 51–54.CrossRefGoogle Scholar
  102. [102]
    Quesada-Chanto, A., A. S. Afschar, and F. Wagner (1994) Microbial production of propionic acid and vitamin B12 using molasses or sugar.Appl. Microbiol. Biotechnol. 41: 378–383.Google Scholar
  103. [103]
    Hartlep, M., W. Hussmann, N. Prayitno, I. Meynial-Salles, P. P. Zeng (2002) Study of two stage processes for the microbial production of 1,3-propanediol from glucose.Appl. Microbiol. Biotechnol. 60: 60–66.CrossRefGoogle Scholar
  104. [104]
    Neumann, E., S. Mueller, E. Butter, B. Fengler, P. Kramer, H. Koellner, R. Kuenstler, J. Ludwig, and H. Haeckert (1989) Isolation of gibberellins from culture filtrate.Patent No. DD-266591.Google Scholar
  105. [105]
    Koellner, H., J. Ludwig, H. W. Leonhard, E. Neumann, D. Paul, G. Kerns, and J. Steffen (1990) Isolation and purification of gibberellic acid from culture media. Patent No. DD 282,241.Google Scholar
  106. [106]
    Li, Z., J. Lei, and D. Zhang (1992) Solvent extraction of gibberellin from fermentation filtrate.Patent No. CN 1,063,309.Google Scholar
  107. [107]
    Rachev, R. C., R. Pavlova-Rouseva, S. V. Bojkova, and V. K. Gancheva (1993) Isolation of gibberellic acid produced byF. moniliforme.J. Nat. Products. 56: 1168–1170CrossRefGoogle Scholar
  108. [108]
    Heropolitanski, R., J. M. Kominiak, and M. Machalowska (1994) Method of isolating gibberellins from aqueous solutions.Patent No. PL 163, 608.Google Scholar
  109. [109]
    Kumar, P. K. R., K. U. Sankar, and B. K. Lonsane (1991) Supercritical fluid extraction from dry moldy bran for purification of gibberellic acid from concomitant products produced during SSF.Chem. Eng. J. Biochem. Eng. 46: B53-B58.Google Scholar
  110. [110]
    Kumar, P. K. R. and B. K. Lonsane (1987) Extraction of gibberellic acid from dry mouldy bran produced under solid state fermentation.Proc. Biochem. 22: 139–143.Google Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering 2003

Authors and Affiliations

  • Ruchi Shukla
    • 1
  • Ashok K. Srivastava
    • 1
  • Subhash Chand
    • 1
  1. 1.Department of Biochemical Engineering and BiotechnologyIndian Institute of TechnologyNew DelhiIndia

Personalised recommendations