{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(40)"],"submitter":["Menuhin-Gruman I"],"pubmed_abstract":["Evolutionary instability is a persistent challenge in synthetic biology, often leading to the loss of heterologous gene expression over time. Here, we present STABLES, a gene fusion strategy that links a gene of interest (GOI) to an essential endogenous gene (EG), with a \"leaky\" stop codon in between. This ensures both selective pressure against deleterious mutations and the high expression of the GOI. By leveraging a machine learning framework, we predict optimal GOI-EG pairs on the basis of bioinformatic and biophysical features, identify linkers likely to minimize protein misfolding, and optimize DNA sequences for stability and expression. Experimental validation in <i>Saccharomyces cerevisiae</i> demonstrated substantial improvements in stability and productivity for fluorescent protei"],"journal":["Science advances"],"pagination":["eadx0796"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12487889"],"repository":["biostudies-literature"],"pubmed_title":["AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits."],"pmcid":["PMC12487889"],"pubmed_authors":["Menuhin-Gruman I","Naki D","Bergman S","Arbel-Groissman M","Tuller T"],"additional_accession":[]},"is_claimable":false,"name":"AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.","description":"Evolutionary instability is a persistent challenge in synthetic biology, often leading to the loss of heterologous gene expression over time. Here, we present STABLES, a gene fusion strategy that links a gene of interest (GOI) to an essential endogenous gene (EG), with a \"leaky\" stop codon in between. This ensures both selective pressure against deleterious mutations and the high expression of the GOI. By leveraging a machine learning framework, we predict optimal GOI-EG pairs on the basis of bioinformatic and biophysical features, identify linkers likely to minimize protein misfolding, and optimize DNA sequences for stability and expression. Experimental validation in <i>Saccharomyces cerevisiae</i> demonstrated substantial improvements in stability and productivity for fluorescent protei","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T01:32:51.043Z","creation":"2026-05-03T03:14:10.596Z"},"accession":"S-EPMC12487889","cross_references":{"pubmed":["41032600"],"doi":["10.1126/sciadv.adx0796"]}}