Automated design of thousands of nonrepetitive parts for engineering stable genetic systems

Engineered genetic systems are prone to failure when their genetic parts contain repetitive sequences. Designing many nonrepetitive genetic parts with desired functionalities remains a difficult challenge with high computational complexity. To overcome this challenge, we developed the Nonrepetitive Parts Calculator to rapidly generate thousands of highly nonrepetitive genetic parts from specified design constraints, including promoters, ribosome-binding sites and terminators. As a demonstration, we designed and experimentally characterized 4,350 nonrepetitive bacterial promoters with transcription rates that varied across a 820,000-fold range, and 1,722 highly nonrepetitive yeast promoters with transcription rates that varied across a 25,000-fold range. We applied machine learning to explain how specific interactions controlled the promoters’ transcription rates. We also show that using nonrepetitive genetic parts substantially reduces homologous recombination, resulting in greater genetic stability.

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Work Title Automated design of thousands of nonrepetitive parts for engineering stable genetic systems
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Open Access
Creators
  1. Ayaan Hossain
  2. Eriberto Lopez
  3. Sean Halper
  4. Daniel Philip Cetnar
  5. ALEXANDER CAMP REIS
  6. Devin Strickland
  7. Eric Klavins
  8. Howard Salis
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. Nature Biotechnology
Publication Date July 13, 2020
Subject
  1. Synthetic Biology
Publisher Identifier (DOI)
  1. https://doi.org/10.1038/s41587-020-0584-2
Deposited March 01, 2021

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Version 1
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  • Created
  • Added Creator Ayaan Hossain
  • Added Creator Eriberto Lopez
  • Added Creator Sean Halper
  • Added Creator Daniel Philip Cetnar
  • Added Creator ALEXANDER CAMP REIS
  • Added Creator Devin Strickland
  • Added Creator Eric Klavins
  • Added Creator Howard Salis
  • Added Hossain2020_final_version.pdf
  • Updated Publication Date, License Show Changes
    Publication Date
    • 2020-7-13
    • (2020-7-13)
    License
    • https://creativecommons.org/licenses/by-nc-nd/4.0/
  • Updated Publication Date Show Changes
    Publication Date
    • (2020-7-13)
    • (2020-07-13)
  • Updated Publication Date Show Changes
    Publication Date
    • (2020-07-13)
    • 2020-07-13
  • Published
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