One of the major challenges in sustainable chemistry is expanding the palette of bio-based chemicals that can replace, or at least reduce, the exploitation of fossil fuel–based chemicals. Cell-free metabolic engineering using soluble enzymes is an emerging and versatile approach aimed at increasing the selectivity and productivity of chemical biomanufacturing processes. However, soluble and isolated enzymes face significant limitations in efficiency, stability, and reusability, which hinder their industrial application.
To address these challenges, enzymes can be rationally immobilized on smart materials, yielding robust, efficient, and self-sufficient heterogeneous biocatalysts. Nevertheless, current immobilization strategies are largely limited to simple enzyme cascades. The mission of METACELL is to develop self-sufficient artificial metabolic cells (AMCs) by immobilizing complex metabolic networks onto hierarchical porous materials. To achieve this goal, solid surfaces must play an active role in the chemical process rather than serving merely as passive immobilization supports. These AMCs envision very productive and robust multi-functional heterogeneous biocatalysts to be implemented under industrial settings.
This integrative proposal will combine protein engineering, surface chemistry, bio-organic chemistry, and protein immobilization strategies to enable: (1) the development of a cell-free artificial metabolism; (2) innovative engineering tools to modify both enzyme and material surfaces; and (3) the continuous synthesis of industrially relevant fine chemicals catalyzed by AMCs packed into flow reactors. The resulting METACELL technology will serve as a prototyping platform for testing artificial biosynthetic pathways towards the manufacturing of fine chemicals with applications in polymer, food, and medicinal chemistry. Furthermore, the AMCs herein developed may contribute to expanding the biochemical toolbox of biorefineries. Beyond its technological outcomes, METACELL will generate fundamental insights into how the spatial organization of multi-enzyme systems influences the performance of in vitro biosynthetic pathways confined within artificial chassis based on solid materials.
