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Disulfide-compatible phage-assisted continuous evolution in the periplasmic space

Author

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  • Mary S. Morrison

    (Merkin Institute of Transformative Technologies in Health Care, Broad Institute of Harvard and MIT
    Harvard University
    Harvard University)

  • Tina Wang

    (Merkin Institute of Transformative Technologies in Health Care, Broad Institute of Harvard and MIT
    Harvard University
    Harvard University)

  • Aditya Raguram

    (Merkin Institute of Transformative Technologies in Health Care, Broad Institute of Harvard and MIT
    Harvard University
    Harvard University)

  • Colin Hemez

    (Merkin Institute of Transformative Technologies in Health Care, Broad Institute of Harvard and MIT
    Harvard University
    Harvard University)

  • David R. Liu

    (Merkin Institute of Transformative Technologies in Health Care, Broad Institute of Harvard and MIT
    Harvard University
    Harvard University)

Abstract

The directed evolution of antibodies has yielded important research tools and human therapeutics. The dependence of many antibodies on disulfide bonds for stability has limited the application of continuous evolution technologies to antibodies and other disulfide-containing proteins. Here we describe periplasmic phage-assisted continuous evolution (pPACE), a system for continuous evolution of protein-protein interactions in the disulfide-compatible environment of the E. coli periplasm. We first apply pPACE to rapidly evolve novel noncovalent and covalent interactions between subunits of homodimeric YibK protein and to correct a binding-defective mutant of the anti-GCN4 Ω-graft antibody. We develop an intein-mediated system to select for soluble periplasmic expression in pPACE, leading to an eight-fold increase in soluble expression of the Ω-graft antibody. Finally, we evolve disulfide-containing trastuzumab antibody variants with improved binding to a Her2-like peptide and improved soluble expression. Together, these results demonstrate that pPACE can rapidly optimize proteins containing disulfide bonds, broadening the applicability of continuous evolution.

Suggested Citation

  • Mary S. Morrison & Tina Wang & Aditya Raguram & Colin Hemez & David R. Liu, 2021. "Disulfide-compatible phage-assisted continuous evolution in the periplasmic space," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26279-8
    DOI: 10.1038/s41467-021-26279-8
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    References listed on IDEAS

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    1. Johnny H. Hu & Shannon M. Miller & Maarten H. Geurts & Weixin Tang & Liwei Chen & Ning Sun & Christina M. Zeina & Xue Gao & Holly A. Rees & Zhi Lin & David R. Liu, 2018. "Evolved Cas9 variants with broad PAM compatibility and high DNA specificity," Nature, Nature, vol. 556(7699), pages 57-63, April.
    2. Ahmed H. Badran & David R. Liu, 2015. "Development of potent in vivo mutagenesis plasmids with broad mutational spectra," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    3. Hyun-Soo Cho & Karen Mason & Kasra X. Ramyar & Ann Marie Stanley & Sandra B. Gabelli & Dan W. Denney & Daniel J. Leahy, 2003. "Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab," Nature, Nature, vol. 421(6924), pages 756-760, February.
    4. Ignacio Asial & Yue Xiang Cheng & Henrik Engman & Maria Dollhopf & Binghuang Wu & Pär Nordlund & Tobias Cornvik, 2013. "Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell," Nature Communications, Nature, vol. 4(1), pages 1-8, December.
    5. Nathan Crook & Joseph Abatemarco & Jie Sun & James M. Wagner & Alexander Schmitz & Hal S. Alper, 2016. "In vivo continuous evolution of genes and pathways in yeast," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    6. Kevin M. Esvelt & Jacob C. Carlson & David R. Liu, 2011. "A system for the continuous directed evolution of biomolecules," Nature, Nature, vol. 472(7344), pages 499-503, April.
    7. Ahmed H. Badran & Victor M. Guzov & Qing Huai & Melissa M. Kemp & Prashanth Vishwanath & Wendy Kain & Autumn M. Nance & Artem Evdokimov & Farhad Moshiri & Keith H. Turner & Ping Wang & Thomas Malvar &, 2016. "Continuous evolution of Bacillus thuringiensis toxins overcomes insect resistance," Nature, Nature, vol. 533(7601), pages 58-63, May.
    8. Chad W. Johnston & Ahmed H. Badran & James J. Collins, 2020. "Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    9. Bryan C. Dickinson & Michael S. Packer & Ahmed H. Badran & David R. Liu, 2014. "A system for the continuous directed evolution of proteases rapidly reveals drug-resistance mutations," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
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