⮝ Full datasets listing
PXD050905
PXD050905 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Synthetic genomes unveil the effects of synonymous recoding |
| Description | Engineering the genetic code of an organism provides the basis for 1: making any organism safely resistant to natural viruses and 2: preventing genetic information flow into and out of genetically modified organisms while 3: allowing the biosynthesis of genetically encoded unnatural polymers. Achieving these three goals requires the reassignment of multiple of the 64 codons nature uses to encode proteins. However, synonymous codon replacement recoding is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using whole-genome synthesis, multiplexed directed evolution, and genome transcriptome-translatome-proteome-co-profiling on multiple recoded genomes. Using this information, we construct an Escherichia coli genome that uses 57 codons to encode protein synthesis and assemble this synthetic genome in seven sections. By discovering the rules responsible for the lethality of synonymous recoding and developing a data-driven multi-omics-based genome construction workflow that troubleshoots synthetic genomes, we overcome the lethal effects of 62,007 synonymous codon swaps and 11,108 additional genomic edits. We show that synonymous recoding induces transcriptional noise including new antisense RNAs, leading to drastic transcriptome and proteome perturbation. As the elimination of select codons from an organisms genetic code results in the widespread appearance of cryptic promoters, we show that synonymous codon choice may naturally evolve to minimize transcriptional noise. Our work provides the first genome scale description of how synonymous codon changes influence organismal fitness and paves the way for the construction of functional genomes that provide genetic firewalls from natural ecosystems and safely produce biopolymers, drugs, and enzymes with an expanded chemistry. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-04-20 |
| AnnouncementXML | Submission_2026-04-20_09:47:23.884.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Bogdan Budnik |
| SpeciesList | scientific name: Escherichia coli; common name: E. coli; NCBI TaxID: 562; |
| ModificationList | Oxidation |
| Instrument | instrument model |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-03-22 09:18:22 | ID requested | |
| ⏵ 1 | 2026-04-20 09:47:24 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: synthetic genomes, genetically encoded unnatural polymers, codon replacement |
Contact List
| George M Church | |
|---|---|
| contact affiliation | Harvard Medical School |
| contact email | gchurch@genetics.med.harvard.edu |
| lab head | |
| Bogdan Budnik | |
| contact affiliation | Harvard University |
| contact email | Bogdan.Budnik@wyss.harvard.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v07/MSV000094380/ |
