Journal
SCIENCE
Volume 353, Issue 6301, Pages 819-822Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf3639
Keywords
-
Categories
Funding
- U.S Department of Energy [DE-FG02-02ER63445]
- Defense Advanced Research Projects Agency [BAA-12-64]
- NSF [106394]
- DOD NDSEG Fellowship
- NSF Graduate Research Fellowship
- Origins of Life Initiative at Harvard University
Ask authors/readers for more resources
Recoding-the repurposing of genetic codons-is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available