|EntreChem participates in the synthetic biology project «STREPSYNTH»
January 8th, 2014 - Oviedo (Spain)
||EntreChem participates in the FP7 European Collaborative Project STREPSYNTH, whose goal is rewiring Streptomyces bacteria as a cell factory for the cost-effective production of biomolecules. The project has been awarded in the last KBBE-FP7 call that focused on synthetic biology, a topic of current high interest both in industry and academia.
||The project, led by the Katholieke University of Leuven (KU Leuven, Leuven, Belgium) enrolls 16 partners (4 SMEs, 7 academic partners and 5 research organizations), a global budget of 11MEUR (8M financed by the European Comission), and will run for 5 years. EntreChem obtains a commitment of 0,6M EUR from the EU. The funds will help develop novel Streptomyces bacterial strains, using advanced genetic engineering, that will allow high yield production of a variety of fermentation molecules, in the case of EntreChem bioactive hybrid natural products used in the development of new oncology drugs.
STREPSYNTH aims to set-up a Streptomyces-based new industrial production platform (SNIP) for high value added biomolecules. Streptomyces lividans was chosen as a bacterial host cell because it has been already shown to be highly efficient for the extracellular production of a number of heterologous molecules that vary chemically; has a robust tradition of industrial fermentation and is fully accessible to genetic intervention.
To develop SNIP our strategy has two components: first, we will construct a collection of reduced-genome S. lividans strains. This will metabolically streamline the cell and rid it of agents (e.g. proteases, secondary metabolites) that may potentially hamper the production of the aimed heterologous molecules. Second, we will engineer synthetic parts and cassettes, i.e. reshuffled, rewired and repurposed genetic elements either indigenous to S. lividans or clusters of heterologous genes organized in artificial operons. These elements will serve three aims: transcriptional and translational optimization, sophisticated on-demand transcriptional regulation that will provide unique fermentation control and metabolic engineering of complete cellular pathways that will channel biomolecules to extracellular secretion. Synthetic parts and cassettes will be either directly incorporated into the genome or be hosted in the form of plasmids. Systems biology tools will guide fine-tuning rounds of cell factory engineering and fermentation optimization.
To set up SNIP, we chose two classes of biomolecules with obvious immediate industrial value and application: heterologous proteins (industrial enzymes, biopharmaceuticals, biofuel enzymes, diagnostics) and small molecules (lantipeptides and indolocarbozoles) useful for multiple industrial purposes (biopharmaceuticals, additives, food technology, bioenergy). The assembly of non-natural building blocks, e.g. non-proteinogenic amino acids, into these biomolecules will be addressed. These biomolecules are of immediate interest to SMEs that participate and guide the industrial relevance of STREPSYNTH. SNIP is a modular platform that can be repurposed for diverse future applications.