Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology.

Autor: Radde N; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Mortensen GA; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Bhat D; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Shah S; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Clements JJ; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Leonard SP; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., McGuffie MJ; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA., Mishler DM; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.; The Freshman Research Initiative, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA., Barrick JE; Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA. jbarrick@cm.utexas.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 24; Vol. 15 (1), pp. 6242. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1038/s41467-024-50639-9
Abstrakt: Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Escape mutants that alleviate this burden can rapidly evolve and take over cell populations, making genetic engineering less reliable and predictable. Synthetic biologists often use genetic parts encoded on plasmids, but their burden is rarely characterized. We measured how 301 BioBrick plasmids affected Escherichia coli growth and found that 59 (19.6%) were burdensome, primarily because they depleted the limited gene expression resources of host cells. Overall, no BioBricks reduced the growth rate of E. coli by >45%, which agreed with a population genetic model that predicts such plasmids should be unclonable. We made this model available online for education ( https://barricklab.org/burden-model ) and added our burden measurements to the iGEM Registry. Our results establish a fundamental limit on what DNA constructs and genetic modifications can be successfully engineered into cells.
(© 2024. The Author(s).)
Databáze: MEDLINE
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