<i>De Novo</i> Autogenic Engineered Living Functional Materials

ABSTRACT Autogenic engineered living materials (ELMs) enable the in situ production and engineering of native extracellular matrix (ECM). However, existing autogenic ELMs remain limited in scope and functionality. Here, we present a versatile platform for de novo autogenic functional ELMs, leveraging protein mining, computational modeling, and synthetic biology. By analyzing 33,564 CsgA‐like homologs, we identify candidates for de novo ECM protein nanofibers. Using AlphaFold2 and molecular dynamics simulations, we elucidate the structural stability of these β‐solenoid proteins. By reprogramming the Escherichia coli curli machinery, we achieve the biosynthesis of CsgA‐like ELMs from non‐model bacteria, featuring up to a 9‐fold increased molecular weight and expanded β‐sheet repeat units. Furthermore, we fabricate macroscopic biomaterials with enhanced mechanical properties (a 3‐fold increase in storage modulus), and their extracellular fiber networks attenuate UV‐C irradiation, extending the survival of embedded cells by 5‐fold. We further demonstrate programmable functionalities, including 3D printability and selective binding to nanoparticles and antibodies. This work establishes a powerful framework for discovering, designing, and harnessing natural biomolecular systems to advance next‐generation autogenic ELMs.