Increased heterologous protein production by Saccharomyces cerevisiae growing on ethanol as sole carbon source

Saccharomyces cerevisiae is a widely used host organism for the production of heterologous proteins, often cultivated in glucose‐based fed‐batch processes. This production system however has many factors limiting the productivity, mainly towards the end of the fermentation. For the optimised product...

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Bibliographic Details
Published in:	Biotechnology and bioengineering Vol. 96; no. 3; pp. 483 - 494
Main Authors:	van de Laar, Teun, Visser, Chris, Holster, Marianne, López, Cristina García, Kreuning, Dennes, Sierkstra, Laurens, Lindner, Nigel, Verrips, Theo
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2007 Wiley
Subjects:	Animals Biological and medical sciences Bioreactors Biotechnology Camelids, New World - genetics carbon source ethanol Ethanol - metabolism fermentation Fundamental and applied biological sciences. Psychology heterologous protein Immunoglobulin Heavy Chains - biosynthesis Immunoglobulin Heavy Chains - genetics Immunoglobulin Variable Region - biosynthesis Immunoglobulin Variable Region - genetics Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - growth & development secretion Fungi Yeast Ethanol Secretion Production Ascomycetes Recombinant protein carbon source Fermentation heterologous protein Saccharomyces cerevisiae Thallophyta
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Summary:	Saccharomyces cerevisiae is a widely used host organism for the production of heterologous proteins, often cultivated in glucose‐based fed‐batch processes. This production system however has many factors limiting the productivity, mainly towards the end of the fermentation. For the optimised production of a Camelid antibody fragment this process was evaluated. In shake flask cultivations, it was found that ethanol has a strong effect on productivity increase and therefore glucose and ethanol fed‐batch fermentations were compared. It appeared that specific heterologous protein production was up to five times higher in the ethanol cultivation and could be further optimised. Then the key characteristics of ethanol fed‐batch fermentations such as growth rate and specific production were determined under ethanol limitation and accumulation and growth limiting conditions in the final phase of the process. It appeared that an optimal production process should have an ethanol accumulation throughout the feed phase of approximately 1% v/v in the broth and that production remains very efficient even in the last phase of the process. This productivity increase on ethanol versus glucose was also proven for several other Camelid antibody fragments some of which were heavily impaired in secretion on glucose, but very well produced on ethanol. This leads to the suggestion that the ethanol effect on improved heterologous protein production is linked to a stress response and folding and secretion efficiency. Biotechnol. Bioeng. 2007;96: 483–494. © 2006 Wiley Periodicals, Inc.
Bibliography:	ArticleID:BIT21150 istex:63D8D7F94C2CF2F87A6D5676F19B0F3514528D99 ark:/67375/WNG-RC7JVVH2-1 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0006-3592 1097-0290
DOI:	10.1002/bit.21150