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Systems biology strategies and metabolome engineering for the enhanced production of recombinant proteins in streptomyces

Objective

Streptomyces has been shown to be an invaluable host for the secretory production of biopharmaceuticals and other heterologous proteins. STREPTOMICS aims to further evaluate this host as a cell factory for the industrial production of proteins of diverse origin including from mammalians, bacteria and archeae of interest for human health and environment. To enhance production, STREPTOMICS will combine genomic data, metabolic network modelling, metabolic flux analysis and proteomics. This systems biology approach will identify genes/proteins with key roles in protein secretion and their interrelationship with cell growth, secretion stress control and energy production/consumption. In addition, some key proteins of the secretion machinery, which may hinder efficient secretion of heterologous proteins, will be investigated. Based on fundamental research of these key proteins to allow rational mutations, also directed evolution, which provides an ideal system to create a protein with optimized properties, in this case for improved secretion, will be performed. Based on the obtained information and modulation, a 'toolbox' of strains will be appropriately engineered and further developed by these state-of-the art approaches such that they optimally over-secrete during fermentation.
Hence, the obtained deliverables will permit the targeted manipulation of specific metabolic pathways and the modulation of key proteins of the protein secretion pathway. As a result of better understanding of the metabolome-secretome interplay strategies for improved protein secretion will be designed. These will combine better energy generation and directed energy consumption for either cell mass production or heterologous protein secretion. Successful realisation of the objectives of the project will therefore provide useful and commercially valuable innovation to the EU Streptomyces protein production platform'.

Call for proposal

FP6-2005-LIFESCIHEALTH-7
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Funding Scheme

STREP - Specific Targeted Research Project
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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Address
Oude Markt 13
Leuven
Belgium

Participants (9)

ERNST-MORITZ-ARNDT-UNIVERSITAT GREIFSWALD
Germany
Address
Domstr.14
Greifswald
DIREVO BIOTECH AG
Germany
Address
Nattermannallee 1
Cologne (Koeln)
FOUNDATION OF RESEARCH AND TECHNOLOGY-HELLAS
Greece
Address
Vassilika Vouton
1385 Iraklio
EUROGENTEC S.A.
Belgium
Address
Liege Science Park, Rue Bois Saint Jean 5
Seraing
PROKARIA
Iceland
Address
Skulagata 5
Reykjavik
BIOXPR S.A.
Belgium
Address
Rue Du Seminaire, 22
Namur
THE UNIVERSITY OF MANCHESTER
United Kingdom
Address
Oxford Road
Manchester
TECHNICAL UNIVERSITY OF DENMARK
Denmark
Address
Anker Engelunds Vej 1
Kgs. Lyngby
GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LTD
United Kingdom
Address
980 Great West Road
Brentford