Extracellular production of an intact and biologically active human growth hormone by the Bacillus brevis system |
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Authors: | T Kajino Y Saito O Asami Y Yamada M Hirai S Udata |
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Institution: | (1) Toyota Central Research & Development Laboratories Inc, Aichi, Japan, JP;(2) Department of Brewing and Fermentation, Faculty of Agriculture, Tokyo University of Agriculture, Tokyo, Japan, JP |
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Abstract: | The characteristic features of the Bacillus brevis system are very high productivity of heterologous proteins and very low extracellular protease activity. However, degradation
of some heterologous proteins, especially mammalian proteins, can be observed and resulted in a lowering of protein productivity.
By using a mutant expressing low levels of proteases and the addition of EDTA to the medium, intact human growth hormone
(hGH) was successfully produced with the B. brevis system. Signal peptide modification with higher basicity in the amino terminal region and higher hydrophobicity in the middle
region brought about a twelve-fold increase in hGH production. The hGH yield was further elevated to 240 mg L−1 by optimization of culture conditions. Thus, biologically active and mature hGH can be efficiently produced directly in
the medium with the B. brevis system.
Received 06 March 1997/ Accepted in revised form 03 July 1997 |
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Keywords: | : human growth hormone Bacillus brevis secretion protease inhibitor |
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