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Regulation of heparinase synthesis in Flavobacterium heparinum

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Abstract

The effect of various carbon, nitrogen and sulfur sources on the production of heparinase by Flavobacterium heparinum in defined medium in the presence and absence of heparin as the inducer has been studied. Carbon catabolite repression has been observed in defined medium containing one of several carbon sources including simple sugars, alcohols and organic acids. Fed batch fermentations result in 10 g/l of cells and heparinase titers as high as 100,000 U/l by avoiding carbon catabolite repression. Growth on heparin as a sole carbon source resulted in both a high growth rate of 0.12 h−1 and a high specific activity of 18 U/mg. Specific heparinase activity was markedly reduced when the end products of heparin catabolism were used as carbon, nitrogen or sulfur sources in defined medium. In defined medium with a low sulfate concentration, of less than 10−3 M, specific activities as high as 8 U/mg have been observed even in the absence of the normally required inducer, heparin.

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References

  • Bergey's Manual of Determinative Bacteriology, Eighth Edition (1974) Buchanan RE, Gibbons NE (eds) Williams and Wilkins Co, Baltimore, MD, p 362

    Google Scholar 

  • Dietrich CP, Silva ME, Michelacci YM (1973) Sequential Degradation of Heparin in Flavobacterium heparinum. J Biol Chem 248:6408–6415

    Google Scholar 

  • Galliher PM, Cooney CL, Langer R, Linhardt RJ (1981) Heparinase Production by Flavobacterium heparinum. J Appl Environ Microbiol 41:360–365

    Google Scholar 

  • Gornal AG, Bardwill CJ, David MM (1949) Determination of Serum Proteins by Means of the Biuret Reaction. J Biol Chem 177:751–766

    Google Scholar 

  • Kanwar YS, Farquhar MG (1979) Presence of Heparin Sulfate in the Glomerular Basement Membrane. Proc Natl. Acad Sci. USA 76:1303–1307

    Google Scholar 

  • Langer R, Linhardt, RJ, Cooney CL, Klein M, Tapper D, Hoffberg SM, Larsen A (1982a) An Enzymatic System for Removing Heparin in Extracorporeal Therapy Science 217:261–263

    Google Scholar 

  • Langer R, Linhardt RJ, Klein M, Galliher PM, Cooney CL, Flanagan MM (1982b) A System for Heparin Removal. In: Cooper S, Hoffman A, Peppas N, Ratner B (eds) Biomaterials: Interfacial Phenomenon and Applications, Advances in Chemistry Series. Washington, DC, p 493–509

  • Lindahl U, Backstrom G, Hook M, Thunberg L, Fransson L, Linker A (1979) Structure of the Antithrombin-Binding Site in Heparin. Proc Natl. Acad. Sci. USA 76:3198–3202

    Google Scholar 

  • Linhardt RJ, Grant A, Cooney CL, Langer R (1982a) Differential Anticoagulant Activity of Heparin Fragments Prepared Using Microbial Heparinase. J Biol Chem 257:7310–7313

    Google Scholar 

  • Linhardt RJ, Fitzgerald GL, Cooney CL, Langer R (1982b) Mode of Action of Heparin Lyase E.C. 4.2.2.7. on Heparin. Biochem Biophys Acta 702:197–203

    Google Scholar 

  • Linker A, Hovingh P (1972) Heparinase and Heparitinase from Flavobacteria. Methods Enzymol 28:902–911

    Google Scholar 

  • Miller GL (1959) Use of Dinitrosalicylic Acid Reagent for Determination of Reducing Sugar. Anal Chem 31:426–428

    Google Scholar 

  • Payza AN, Korn ED (1956) Bacterial Degradation of Heparin. Nature 177:88–89

    Google Scholar 

Download references

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Galliher, P.M., Linhardt, R.J., Conway, L.J. et al. Regulation of heparinase synthesis in Flavobacterium heparinum . European J. Appl. Microbiol. Biotechnol. 15, 252–257 (1982). https://doi.org/10.1007/BF00499966

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  • DOI: https://doi.org/10.1007/BF00499966

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