Efficient protein production inspired by how spiders make silk

Nina Kronqvist (), Médoune Sarr, Anton Lindqvist, Kerstin Nordling, Martins Otikovs, Luca Venturi, Barbara Pioselli, Pasi Purhonen, Michael Landreh, Henrik Biverstål, Zigmantas Toleikis, Lisa Sjöberg, Carol V. Robinson, Nicola Pelizzi, Hans Jörnvall, Hans Hebert, Kristaps Jaudzems, Tore Curstedt, Anna Rising and Jan Johansson
Additional contact information
Nina Kronqvist: Center for Alzheimer Research, Karolinska Institutet
Médoune Sarr: Center for Alzheimer Research, Karolinska Institutet
Anton Lindqvist: Spiber Technologies AB
Kerstin Nordling: Center for Alzheimer Research, Karolinska Institutet
Martins Otikovs: Latvian Institute of Organic Synthesis
Luca Venturi: Chiesi Farmaceutici, Largo Belloli 11/A
Barbara Pioselli: Chiesi Farmaceutici, Largo Belloli 11/A
Pasi Purhonen: Karolinska Institutet, and School of Technology and Health, KTH Royal institute of Technology
Michael Landreh: Physical and Theoretical Chemistry Laboratory, University of Oxford
Henrik Biverstål: Center for Alzheimer Research, Karolinska Institutet
Zigmantas Toleikis: Latvian Institute of Organic Synthesis
Lisa Sjöberg: Center for Alzheimer Research, Karolinska Institutet
Carol V. Robinson: Physical and Theoretical Chemistry Laboratory, University of Oxford
Nicola Pelizzi: Chiesi Farmaceutici, Largo Belloli 11/A
Hans Jörnvall: Karolinska Institutet
Hans Hebert: Karolinska Institutet, and School of Technology and Health, KTH Royal institute of Technology
Kristaps Jaudzems: Latvian Institute of Organic Synthesis
Tore Curstedt: Karolinska Institutet at Karolinska University Hospital
Anna Rising: Center for Alzheimer Research, Karolinska Institutet
Jan Johansson: Center for Alzheimer Research, Karolinska Institutet

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Membrane proteins are targets of most available pharmaceuticals, but they are difficult to produce recombinantly, like many other aggregation-prone proteins. Spiders can produce silk proteins at huge concentrations by sequestering their aggregation-prone regions in micellar structures, where the very soluble N-terminal domain (NT) forms the shell. We hypothesize that fusion to NT could similarly solubilize non-spidroin proteins, and design a charge-reversed mutant (NT*) that is pH insensitive, stabilized and hypersoluble compared to wild-type NT. NT*-transmembrane protein fusions yield up to eight times more of soluble protein in Escherichia coli than fusions with several conventional tags. NT* enables transmembrane peptide purification to homogeneity without chromatography and manufacture of low-cost synthetic lung surfactant that works in an animal model of respiratory disease. NT* also allows efficient expression and purification of non-transmembrane proteins, which are otherwise refractory to recombinant production, and offers a new tool for reluctant proteins in general.

Date: 2017
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DOI: 10.1038/ncomms15504

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