Project: Enzyme Production in Optimized Streptomyces.
The exponentially growing demand for enzymes with the increasing human population, and the exponential growth of new economies sets new demands on modern biotechnology. These materials need to be provided in a sustainable manner, with less dependency on non-renewable fossil resources. In industrial biotechnology the production of enzymes for sustainable and eco-efficient technologies in the textile-, paper-, consumer- and biofuel applications is a key objective. New enzyme production platforms must provide more choice and open up previously untapped enzyme sources. Due to their saprophytic nature streptomycetes contain a massive arsenal of industrial enzymes, including amylases, proteases, cellulases, xylanases and esterases. However, so far their use as industrial production platform is relatively limited, due to their slow mycelial growth, inefficient nutrient utilization and the lack of advanced expression systems. Other efficient enzyme production hosts (e.g. E. coli, B. subtilis) are currently used in the industry and via a plug-bug approach several of the Streptomyces enzymes can be expressed heterologously in such systems. However, the majority of the proteins requires host-specific machinery for folding, modification and/or secretion and can therefore not be produced in a bio-active form in other host systems. We will develop the industrially preferred enzyme producer Streptomyces lividans for optimal production of industrial enzymes, using xylanase as the model system. Integrating the latest know-how, the project will tackle the suboptimal parts of the existing production pathway, related to expression (transcription/translation), to secretion (machinery, signals), to the stability of the expressed protein, and to the organism itself (morphological engineering). To reach these objectives a consortium is set up consisting of academic institutions, located in four countries, with ample experience in industrial projects, and involving the relevant industry. The outcome of this project is a new production platform consisting of a strain/vector combination capable of industrial level protein production and secretion. The Streptomyces production host has an optimal fermentation behavior, extended production growth phase, enhanced protein production and secretion capacity and strongly reduced protease activity. The developed expression vectors have the best available transcription, translation and secretion sequences. Strains, expression systems and combinations of the two will be presented to the industry for exploitation after the project. Already existing formal and informal contacts of the partners with interested industrial parties will pave the way for this approach.
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