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

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.