Artificial metabolic cells for biomanufacturing of bio-based chiral fine chemicals

ended

One of the major challenges of sustainable chemistry is expanding the palette of bio-based chemicals that can replace, or at least ameliorate, the exploitation of fuel-based chemicals. Cell-free metabolic engineering using soluble enzymes is an emerging and versatile approach that seeks to increase the selectivity and productivity of chemical biomanufacturing processes. However, soluble and isolated enzymes present major issues in terms of efficiency, stability and re-usability that hamper industrial applications. To solve these problems, enzymes can be rationally immobilized on smart materials resulting in robust, efficient and self-sufficient heterogeneous biocatalysts, but immobilization is still restricted to simple enzyme cascades. METACELL mission is developing self-sufficient artificial metabolic cells (AMCs) by immobilizing complex metabolic networks on hierarchical porous materials. To this aim, the solid surfaces must play an active role in the chemical process rather than just being a mere immobilization support. This integrative proposal will exploit protein engineering, surface chemistry, bio-organic chemistry and protein immobilization tools for the successful development of 1) a cell-free artificial metabolism, 2) innovative engineering tools to modify both enzyme and material surfaces and 3) continuous synthesis of industrially relevant fine chemicals catalyzed by AMCs packed into flow reactors. The resulting technology of METACELL will serve as a prototyping platform to test artificial biosynthetic pathways with application in combinatorial chemistry (e.g drugs discovery). METACELL may also offer long-term solutions for the on-demand production of drugs at the point-of-care. In addition to the technological outputs, METACELL will also provide essential information to understand how spatial organization of multi-enzyme systems affect the performance of in vitro biosynthetic pathways confined into artificial chassis (solid materials).