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QLK3-1999-00413
Engineering of cellular quality control systems in Bacillus subtilis for the production of high value-added proteins |
| Contract No: | QLK3-1999-00413 |
| Project Type: | RS (Research and Technological Development Project) |
| Start Date: | 01-01-2000 |
| Duration: | 36 months |
| Total Cost: | |
| EC Contribution: | 3 091 905 EUR |
| Scientific Officer: |
Abstract
The Bacillus protein secretion machine contains cellular quality control systems that efficienly remove misfolded or incompletely synthesised proteins, making bacilli preferred production organisms for high quality enzymes and high value-added eukaryotic proteins. The partnership proposes to develop rapid and accurate techniques for identifying and overcoming specific production bottlenecks for the secretion of high value-added heterologous proteins that are currently either recovered in low quality and/or at low concentrations. Full use will be made of recent advances in genomics (e.g. DNA arrays), proteomics, bioinformatics, directed molecular evolution and information obtained from previous, EU-funded programmes on Bacillus protein secretion, genome sequencing and the systematic gene function analysis.
Objectives
The objective is to provide efficient systems for the production of high value-added proteins of high quality at commercially significant yields. The quality control machine of the Bacillus cell (BACELL) factory will be identified and engineered. This will involve the analysis of the key components of the Bacillus secretome, comprising the components of the protein secretion pathway and native secretory proteins. The proposed research will build upon previous work by the partnership that has successfully identified key bottlenecks in the secretory pathway of Bacillus. This will lead to deliverables including a "Tool Box" of strategies and strains, improved technical expertise, highly qualified scientists, and European-owned intelectual property protected by patents, improving the competitiveness of European biotechnology and pharmaceutical industries.
Description of the work
The programme is divided into four workpackages:
Workpackages 2 and 4 focus on activities in the cytoplasm and cell envelope that are important in modulating the stability and quality of secretory proteins, while workpackage 3 focuses on the channel that connects these compartments in a pre-protein specific manner. Workpackage 1 interacts with the other workpackages by focusing on the expression of the secretome. In workpackage 1, strategies based on genomic and proteomic approaches will be used to define secretome components. Optimised expression signals will be developed for secretome components and target proteins. Workpackage 2 will focus on cytoplasmic components of the secretome. In workpackage 3, quality control related interactions between translocase components, pre-proteins and intracellular and extra-cellular quality control systems will be characterised. Workpackage 4 involves engineering of extracytoplasmic components that affect the folding and stability of secreted proteins.
Deliverables
Contacts
Coordinator
Participant
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