LAUSR

Developing new protein-based materials with a programmable assembly is of great scientific interest and technological importance. Inspired by nature's use of post-translational modifications (PTMs) to control the function and location of proteins, we have leveraged lipidation-the PTM of proteins with lipids-to synthesize genetically encoded lipidated proteins with controllable hierarchical assembly. Specifically, we envisioned the combination of two orthogonal lipidation pathways with different regioselectivity and substrate preferences inside E.coli to produce recombinant nanomaterials with distinct lipidation domains at each terminus of proteins. In this study, we demonstrate the orthogonality of N-myristoylation and C-cholesterylation pathways for recombinant production of lipidated proteins with a unique triblock architecture, which is a hydrophilic protein block flanked by two lipid tails, i.e., inverse bolaamphiphiles. Our study indicates that the architecture of lipidated protein and the sequence of the polypeptide can be used to control the hierarchical self-assembly of these materials. We envision this bio-enabled approach yielding unexplored recombinant hybrid biomaterials with tunable nanoscale structure and morphology with applications in nanobiotechnology.