Protein cages are naturally occurring nano- to micro-size hollow particles formed entirely by hierarchical protein self-assembly. This protein shell can provide a distinct environment for guest molecules in biological complexity, of which strategy is widely employed for diverse purposes across different species. Protein cages have also been extensively exploited in the laboratory as ideal platforms for constructing delivery/display vehicles, reaction chambers, and novel nanomaterials. Our research team seeks to uncover the protein cage’s potentials as powerful tools for molecular and synthetic biology. We are preliminarily focusing on a cage-forming lumazine synthase and exploiting and expanding the protein cages through redesign and directed evolution. Namely, current projects are aimed (i) to develop a method for directed evolution of proteins; (ii) to establish a new biotechnology for heterologous protein production; and (iii) to understand the theory underlying the hierarchical assembly for future artificial compartment designs. We anticipate that our protein cage-based biotechnologies will contribute significantly to the development of interdisciplinary research realms ranging from basic biophysics, chemistry to therapeutics.



  1. Connectability of protein cages "Review article", Majsterkiewicz K, Azuma Y and Heddle JG, Nanoscale Adv., 2020, Advance Article. https://doi.org/10.1039/D0NA00227E

  2. Cytoplasmic Glycoengineering Enables Biosynthesis of Nanoscale Glycoprotein Assemblies, Tytgat HLP, Lin C, Levasseur MD, Mock J, Terasaka N, Liebscher N, Azuma Y, Wetter M, Bachmann MF, Hilvert D, Aebi M, and Keys TG, Nat. Commun201910, 5403. https://doi.org/10.1038/s41467-019-13283-2

  3. Tailoring Lumazine Synthase Assemblies for Bionanotechnology “Review article” Azuma Y, Edwardson TGW, and Hilvert D, Chem. Soc. Rev201847, 3543-3557. https://doi.org/10.1039/c8cs00154e

  4. Laboratory Evolution of Virus-like Nucleocapsids from Non-viral Protein Cages Terasaka N, Azuma Y, and Hilvert D, Proc. Natl. Acad. Sci. U. S. A. 2018115, 5432-5437. https://doi.org/10.1073/pnas.1800527115

  5. Substrate Sorting by a Supercharged Nanoreactor Azuma Y, Bader DLV, and Hilvert D, J. Am. Chem. Soc. (ACS editor’s choice) 2018140, 860–863. https://doi.org/10.1021/jacs.7b11210 [Featured in Nat. Catalysis 20181, 94, and J. Am. Chem. Soc. 2018140, 1567]

  6. Diversification of Protein Cage Structure Using Circularly Permuted Subunits Azuma Y, Herger M, and Hilvert D, J. Am. Chem. Soc. 2018140, 558–561. https://doi.org/10.1021/jacs.7b10513

  7. Modular Protein Cages for Size-Selective RNA Packaging in Vivo Azuma Y, Edwardson TGW, Terasaka N, and Hilvert D, J. Am. Chem. Soc. 2018140, 566–569. https://doi.org/10.1021/jacs.7b10798

  8. Enzyme Encapsulation in an Engineered Lumazine Synthase Protein Cage “Book chapter” Azuma Y, and Hilvert D, In Methods Mol. Biol. 20181798, Protein Scaffolds, A. K. Udit (Eds), Humana Press, New York, pp 39-55. https://doi.org/10.1007/978-1-4939-7893-9_4

  9. The C-terminal Peptide of Aquifex aeolicus Riboflavin Synthase Directs Encapsulation of Native and Foreign Guests by a Cage-forming Lumazine Synthase, Azuma Y, Zschoche R, and Hilvert D, J. Biol. Chem. 2017292, 10321–10327. http://doi.org/10.1074/jbc.C117.790311

  10. Quantitative Packaging of Active Enzymes in a Protein Cage, Azuma Y, Zschoche R, Tinzl M, and Hilvert D, Angew. Chem. Int. Ed. (Hot Paper) 201655, 1531-1534. https://doi.org/10.1002/anie.201508414