STREPSYNTH · Rewiring the Streptomyces cell factory for cost-effective production of biomolecules

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) of potential harm to the heterologous polypeptides. Second, we will engineer synthetic parts and cassettes, i.e. reshuffled, rewired and repurposed genetic elements either indigenous to S. lividans or heterologous genes organized in artificial operon clusters. 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 channeling biomolecules to profuse 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). 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.