Engineering Ribosome Traffic: Improving Host Fitness and Titer via Biophysical Modeling

Standard codon optimization often ignores the "cellular cost" of protein production. In this publication, we introduce a generic computational approach to eliminate ribosomal traffic jams, a major bottleneck in protein synthesis. By engineering the kinetics of translation through synonymous mutations, we demonstrate a direct correlation between optimized ribosome allocation and improved host growth rates (fitness).

Key Takeaway: Our algorithms successfully increased protein titers in Saccharomyces cerevisiae by optimizing just a few targeted genes, proving that biophysical modeling of translation can unlock significant production gains in any engineered host.

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https://www.nature.com/articles/s41598-020-78260-y