Bacterial encapsulins as orthogonal compartments for mammalian cell engineering

Felix Sigmund, Christoph Massner, Philipp Erdmann, Anja Stelzl, Hannes Rolbieski, Mitul Desai, Sarah Bricault, Tobias P. Wörner, Joost Snijder, Arie Geerlof, Helmut Fuchs, Martin Hrabĕ de Angelis, Albert J. R. Heck, Alan Jasanoff, Vasilis Ntziachristos, Jürgen Plitzko and Gil G. Westmeyer ()
Additional contact information
Felix Sigmund: Helmholtz Zentrum München, Institute of Biological and Medical Imaging
Christoph Massner: Helmholtz Zentrum München, Institute of Biological and Medical Imaging
Philipp Erdmann: Max Planck Institute of Biochemistry, Department of Structural Biology
Anja Stelzl: Helmholtz Zentrum München, Institute of Biological and Medical Imaging
Hannes Rolbieski: Helmholtz Zentrum München, Institute of Biological and Medical Imaging
Mitul Desai: Massachusetts Institute of Technology, Department of Biological Engineering
Sarah Bricault: Massachusetts Institute of Technology, Department of Biological Engineering
Tobias P. Wörner: Utrecht University, Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences
Joost Snijder: Utrecht University, Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences
Arie Geerlof: Helmholtz Zentrum München, Institute of Structural Biology
Helmut Fuchs: Helmholtz Zentrum München, Institute of Experimental Genetics
Martin Hrabĕ de Angelis: Helmholtz Zentrum München, Institute of Experimental Genetics
Albert J. R. Heck: Utrecht University, Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences
Alan Jasanoff: Massachusetts Institute of Technology, Department of Biological Engineering
Vasilis Ntziachristos: Helmholtz Zentrum München, Institute of Biological and Medical Imaging
Jürgen Plitzko: Max Planck Institute of Biochemistry, Department of Structural Biology
Gil G. Westmeyer: Helmholtz Zentrum München, Institute of Biological and Medical Imaging

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.

Date: 2018
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DOI: 10.1038/s41467-018-04227-3

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