Rational Design of Artificial Protein Platform for the Efficacy of Genetically Fused Functional Peptides

Abstract Coating or tethering biofunctional peptides to material surfaces can enhance their environmental stability and activity, offering a strategy that may advance their translational potential for therapeutic and biotechnological applications. However, conventional peptide attachment approaches, such as synthetic polymer‐peptide conjugation, often face challenges in reproducibility and sequence control, limiting their ability to systematically tune macromolecular properties and elucidate key factors influencing peptide functionality. Here, a rationally designed artificial protein platform that genetically fuses sequences for a material scaffold, biopolymer tether, and functional peptide is developed, enabling reproducible biosynthesis and precise sequence control for tunable macromolecular properties. This platform self‐assembles into thermoresponsive micelles, positioning functional peptides within the corona to support their bioactivity. Bacterial inhibition assays confirm that micelle‐incorporated antimicrobial peptides remain effective in suppressing pathogenic bacterial growth, whereas control protein designs do not. Furthermore, tether sequence modifications allow fine‐tuning of physicochemical properties, expanding micelle stability across a broader temperature range while preserving peptide bioactivity. This genetically engineered all‐in‐one platform is anticipated to overcome the limitations of conventional macromolecule‐peptide conjugation, while its versatile design capability offers an advanced strategy for peptide therapeutics and biomaterials engineering.