Protein yield is tunable by synonymous codon changes of translation initiation sites

Autor: Daniela M. Remus, Paul P. Gardner, Bikash K. Bhandari, Chun Shen Lim, Craig J. van Dolleweerd, Augustine Chen
Rok vydání: 2019
Předmět:
Popis: Recombinant protein production is a widely used technique, yet half of these experiments fail at the expression phase. Failures are expected for 9difficult-to-express9 proteins, but for others, codon bias and mRNA folding have been proposed explanations for variable protein abundance. We question how practical these features are for solving protein expression failures. We discover that the energetics of RNA structure ensembles, which models the 9accessibility9 of translation initiation sites, show the strongest correlation with protein abundance across species. Importantly, accessibility outperforms other features when predicting the outcomes of 11,430 recombinant protein production experiments in Escherichia coli. Furthermore, we show that protein level is tunable by synonymous codon changes of the first few codons that alter accessibility.
Databáze: OpenAIRE