Codon usage modulates the relationship between the burden and yield of protein overexpression

Our model reproduces experimentally observed relationships between codon usage bias, gene expression, and burden for overexpressed proteins. Furthermore, it suggests that more nuanced recoding strategies that seek to match a host's overall codon usage bias are less burdensome and will lead to greater protein yields compared to strategies that simply maximize usage of optimal codons. Increasing the level of mechanistic detail in gene expression models can lead to insights that allow researchers to engineer more optimal cellular systems.