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      Role of cultivation media in the development of yeast strains for large scale industrial use

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          Abstract

          The composition of cultivation media in relation to strain development for industrial application is reviewed. Heterologous protein production and pentose utilization by Saccharomyces cerevisiae are used to illustrate the influence of media composition at different stages of strain construction and strain development. The effects of complex, defined and industrial media are compared. Auxotrophic strains and strain stability are discussed. Media for heterologous protein production and for bulk bio-commodity production are summarized.

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          Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast.

          K. Natarajan, M. R. Meyer, B Jackson … (2001)
          Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.
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            Toward a science of metabolic engineering.

            J Bailey (1991)
            Application of recombinant DNA methods to restructure metabolic networks can improve production of metabolite and protein products by altering pathway distributions and rates. Recruitment of heterologous proteins enables extension of existing pathways to obtain new chemical products, alter posttranslational protein processing, and degrade recalcitrant wastes. Although some of the experimental and mathematical tools required for rational metabolic engineering are available, complex cellular responses to genetic perturbations can complicate predictive design.
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              Auxotrophic yeast strains in fundamental and applied research.

              Jack Pronk (2002)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Microb Cell Fact
                Title: Microbial Cell Factories
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2859
                Publication date Collection: 2005
                Publication date (Electronic): 10 November 2005
                Volume: 4
                Page: 31
                Affiliations
                [1 ]Applied Microbiology, LTH/Lund University, P O Box 124, SE-221 00 Lund, Sweden
                [2 ]Department of Process Engineering, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
                [3 ]Department of Microbiology, Stellenbosch University, Private Bag X1, Stellenbosch
                Article
                Publisher ID: 1475-2859-4-31
                DOI: 10.1186/1475-2859-4-31
                PMC ID: 1316877
                PubMed ID: 16283927
                SO-VID: e3a67694-9a76-4478-9636-2aa6d2b48e6f
                Copyright © Copyright © 2005 Hahn-Hägerdal et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 September 2005
                Date accepted : 10 November 2005
                Categories
                Subject: Review

                ScienceOpen disciplines: Biotechnology
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                ScienceOpen disciplines: Biotechnology

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