PT - JOURNAL ARTICLE AU - Bhandari, Bikash K. AU - Lim, Chun Shen AU - Remus, Daniela M. AU - Chen, Augustine AU - van Dolleweerd, Craig AU - Gardner, Paul P. TI - Protein yield is tunable by synonymous codon changes of translation initiation sites AID - 10.1101/726752 DP - 2021 Jan 01 TA - bioRxiv PG - 726752 4099 - http://biorxiv.org/content/early/2021/02/22/726752.short 4100 - http://biorxiv.org/content/early/2021/02/22/726752.full AB - Recombinant protein production is a key process in generating proteins of interest in the pharmaceutical industry and biomedical research. However, about 50% of recombinant proteins fail to be expressed in a variety of host cells. To address this problem, we modified up to the first nine codons of messenger RNAs with synonymous substitutions and showed that protein levels can be tuned. These modifications alter the ‘accessibility’ of translation initiation sites. We also reveal the dynamics between accessibility, gene expression, and turnovers using a coarse-grained simulation.Competing Interest StatementThe authors have declared no competing interest.