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Nat Commun. 2018 May 18;9(1):1990. doi: 10.1038/s41467-018-04227-3.

Bacterial encapsulins as orthogonal compartments for mammalian cell engineering.

Author information

1
Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
2
Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
3
Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, Munich, 81675, Germany.
4
Department of Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, 82152, Germany.
5
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA.
6
Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, Utrecht, 3584CH, The Netherlands.
7
Snijder Bioscience, Spijkerstraat 114-4, Arnhem, 6828 DN, The Netherlands.
8
Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
9
Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
10
Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA.
11
Department of Nuclear Science & Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA.
12
Chair for Biological Imaging, Technical University of Munich, Ismaninger Straße 22, Munich, 81675, Germany.
13
Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany. gil.westmeyer@tum.de.
14
Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany. gil.westmeyer@tum.de.
15
Department of Nuclear Medicine, Technical University of Munich, Ismaninger Straße 22, Munich, 81675, Germany. gil.westmeyer@tum.de.

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.

PMID:
29777103
PMCID:
PMC5959871
DOI:
10.1038/s41467-018-04227-3
[Indexed for MEDLINE]
Free PMC Article

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