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Content archived on 2024-04-30

Optimization of bacillus as a cell factory

Objective



Bacillus is the industrial host of choice for the high yield production of bacterial enzymes. A number of problems have hampered the expression of heterologous proteins of industrial interest by Bacillus species. The solution to this problem lies to a large extent in the identification and control of factors affecting (a) genetic stability of cloned genes, (b) the expression of economically relevant genes and (c) the amenability of industrial Bacillus strains to recombinant DNA technology. The main objective is to construct Bacillus strains which are more suitable for industrial use, by exploring the interface between the recent findings in bacterial physiology, functional genomics and the applied biotechnology.
The goal of this project is to optimise Bacillus as a cell factory for the production of proteins of industrial and/or biomedical interest and to characterize bottle-necks detected under fermentation conditions. Our objectives are: i) to minimize the genome size of B. subtilis 168, ii) to analyse the factor(s) that govern the amplification of genetic information and its stability, iii) to characterize the factors that control the metabolic fluxes and iv) to optimize controlled gene expression. We propose to remove dispensable loci of the genome of B. subtilis, to direct the consumption of resources to the production of desired products. We will develop tools to increase controlled gene expression with the aim of optimizing Bacilli as a cell factory. The availability of the entire DNA sequence of the B. subtilis genome will be of great help for these purposes. We will engineer the sugar uptake to minimize the load on the metabolic flux in the manipulated strains. The full exploitation derived from such an analysis will be of direct relevance to the competitiveness of biotechnological companies in the European Union.
The proposed project will have an intensive interaction with two other major EU-sponsored Bacillus projects [Protein secretion (EBSG BIO4 CT96 0097) and Systematic Function Analysis of Bacillus subtilis genes (BSFA, BIO4 CT95 0278). The involvement of some of the participants of these EU-sponsored projects in this proposal guarantees an optimal interaction between the projects and will result in reciprocal benefits.

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Coordinator

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
EU contribution
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Address
Universidad Autonoma de Madrid, Cantoblanco
28049 MADRID
Spain

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Participants (5)

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