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Highly active enzymes by automated combinatorial backbone assembly and sequence design

Author

Listed:
  • Gideon Lapidoth

    (Weizmann Institute of Science)

  • Olga Khersonsky

    (Weizmann Institute of Science)

  • Rosalie Lipsh

    (Weizmann Institute of Science)

  • Orly Dym

    (Weizmann Institute of Science)

  • Shira Albeck

    (Weizmann Institute of Science)

  • Shelly Rogotner

    (Weizmann Institute of Science)

  • Sarel J. Fleishman

    (Weizmann Institute of Science)

Abstract

Automated design of enzymes with wild-type-like catalytic properties has been a long-standing but elusive goal. Here, we present a general, automated method for enzyme design through combinatorial backbone assembly. Starting from a set of homologous yet structurally diverse enzyme structures, the method assembles new backbone combinations and uses Rosetta to optimize the amino acid sequence, while conserving key catalytic residues. We apply this method to two unrelated enzyme families with TIM-barrel folds, glycoside hydrolase 10 (GH10) xylanases and phosphotriesterase-like lactonases (PLLs), designing 43 and 34 proteins, respectively. Twenty-one GH10 and seven PLL designs are active, including designs derived from templates with

Suggested Citation

  • Gideon Lapidoth & Olga Khersonsky & Rosalie Lipsh & Orly Dym & Shira Albeck & Shelly Rogotner & Sarel J. Fleishman, 2018. "Highly active enzymes by automated combinatorial backbone assembly and sequence design," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05205-5
    DOI: 10.1038/s41467-018-05205-5
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