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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.


Lumazine Synthase Protein Nanocompartments "Book chapter"
Koziej L, Gawin A, and Azuma Y
In Microbiology Monographs, Microbial Production of High-Value Products 2022, 37, Wibowo D and Rehm BHA (Eds), Springer-Nature Switzerland AG, Cham, pp335-355 []

Chemically Induced Protein Cage Assembly with Programmable Opening and Cargo Release 
Stupka I, Azuma Y, Biela AP, Imanura M, Pyza E, Wożnicka O, Maskell DP, and Heddle JG
Sci. Adv. 2022, 8, abj9424 [doi: 10.1126/sciadv.abj9424]   

Connectability of Protein Cages "Review article"
Majsterkiewicz K, Azuma Y and Heddle JG
Nanoscale Adv., 2020, 2, 2255-2264[doi: 10.1039/D0NA00227E]

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. Commun. 2019, 10, 5403. [doi: 10.1038/s41467-019-13283]

Tailoring Lumazine Synthase Assemblies for Bionanotechnology “Review article”
Azuma Y, Edwardson TGW, and Hilvert D
Chem. Soc. Rev. 2018, 47, 3543-3557. [doi: 10.1039/c8cs00154e]

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. 2018, 115, 5432-5437. [doi: 10.1073/pnas.180052711]

Substrate Sorting by a Supercharged Nanoreactor
Azuma Y, Bader DLV, and Hilvert D
J. Am. Chem. Soc. (ACS editor’s choice) 2018, 140, 860–863. [doi: 10.1021/jacs.7b11210]
[Featured in Nat. Catalysis 2018, 1, 94, and J. Am. Chem. Soc. 2018, 140, 1567]

Diversification of Protein Cage Structure Using Circularly Permuted Subunits
Azuma Y, Herger M, and Hilvert D
J. Am. Chem. Soc. 2018, 140, 558–561. [doi: org/10.1021/jacs.7b1051]

Modular Protein Cages for Size-Selective RNA Packaging in Vivo
Azuma Y, Edwardson TGW, Terasaka N, and Hilvert D
J. Am. Chem. Soc. 2018, 140, 566–569. [doi: 10.1021/jacs.7b1079]

Enzyme Encapsulation in an Engineered Lumazine Synthase Protein Cage “Book chapter”
Azuma Y, and Hilvert D
In Methods Mol. Biol. 2018, 1798, Protein Scaffolds, A. K. Udit (Eds), Humana Press, New York, pp 39-55. [doi: 10.1007/978-1-4939-7893-9_4]

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. 2017, 292, 10321–10327. [doi: 10.1074/jbc.C117.79031]

Quantitative Packaging of Active Enzymes in a Protein Cage
Azuma Y, Zschoche R, Tinzl M, and Hilvert D
Angew. Chem. Int. Ed. (Hot Paper) 2016, 55, 1531-1534. [doi: 10.1002/anie.20150841]

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