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
Christoph Massner: Helmholtz Zentrum München
Philipp Erdmann: Max Planck Institute of Biochemistry
Anja Stelzl: Helmholtz Zentrum München
Hannes Rolbieski: Helmholtz Zentrum München
Mitul Desai: Massachusetts Institute of Technology
Sarah Bricault: Massachusetts Institute of Technology
Tobias P. Wörner: Utrecht University
Joost Snijder: Utrecht University
Arie Geerlof: Helmholtz Zentrum München
Helmut Fuchs: Helmholtz Zentrum München
Martin Hrabĕ de Angelis: Helmholtz Zentrum München
Albert J. R. Heck: Utrecht University
Alan Jasanoff: Massachusetts Institute of Technology
Vasilis Ntziachristos: Helmholtz Zentrum München
Jürgen Plitzko: Max Planck Institute of Biochemistry
Gil G. Westmeyer: Helmholtz Zentrum München

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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