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Title of Journal: Appl Microbiol Biotechnol

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Abbravation: Applied Microbiology and Biotechnology

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Springer-Verlag

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DOI

10.1002/hrm.3930040203

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1432-0614

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Increased Hepatitis B surface antigen production b

Authors: Emmanuel R James Willem H van Zyl Johann F Görgens
Publish Date: 2007/02/17
Volume: 75, Issue: 2, Pages: 279-288
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Abstract

The capacity of the filamentous fungi Aspergillus niger to produce and assemble complex immunogenic viral proteins into viruslike particles VLPs in batch culture was enhanced by optimizing the bioprocessing parameters agitation intensity and dissolved oxygen dO2 concentration Response surface methodology RSM and a twofactortwolevel central composite rotatable design CCRD were employed to evaluate the interactive response pattern between parameters and their optimum combination The recombinant hepatitis B surface antigen HBsAg was used as a model VLP system to determine the effect of these parameters on biomass yield fungal morphology HBsAg production and bioreactor kinetics The response surface model predicted optimum cultivation conditions at an agitation of rate of 100 rpm and a dO2 concentration of 25 obtaining highest intracellular membraneassociated HBsAg levels of text3text4textmgtextltext 1 textculture HBsAg production levels were increased tenfold compared to yields obtained in shake flask cultivation Although hepatitis B VLPs mostly accumulated intracellularly optimal bioreactor conditions resulted in significant HBsAg release in culture supernatant These results compare favourably with other recombinant VLP systems in batch culture and therefore indicate a substantial potential for further engineering of the A niger production system for the high level of intracellular and extracellular VLP production

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