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bioRxiv · 10.1101/294173

Synonymous lysine codon usage modification in a mobile antibiotic resistance gene similarly alters protein production in bacterial species with divergent lysine codon usage biases because it removes a duplicate AAA lysine codon.

Alorabi, M.·AlAmri, A. M.·Takbayashi, Y.·Heesom, K. J.·Avison, M.
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Abstract

The mobile antibiotic resistance gene blaIMP-1 is clinically important and has a synonymous AAA:AAG lysine codon usage bias of 73:27. This bias is like that seen in experimentally determined highly expressed genes in Escherichia coli and Acinetobacter baumanii, but quite different from that seen in Pseudomonas aeruginosa (26:74 AAA:AAG). Here we show that, paradoxically, shifting the AAA:AAG lysine codon bias to 8:92 in blaIMP-1 expressed from a natural promoter results in significantly more IMP-1 production in all three species. Sequential site directed mutagenesis revealed that increased IMP-1 production occurs following removal of an AAA,AAA double lysine codon and that otherwise, lysine codon usage had no observable impact on IMP-1 production. We conclude that ribosomal slippage at this poly-adenosine region reduces efficient translation of IMP-1 and that punctuating the region with guanine reduces ribosomal slippage and increases IMP-1 production.

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Alorabi, M., AlAmri, A. M., Takbayashi, Y., Heesom, K. J., Avison, M.. 2018-04-03. Synonymous lysine codon usage modification in a mobile antibiotic resistance gene similarly alters protein production in bacterial species with divergent lysine codon usage biases because it removes a duplicate AAA lysine codon.. https://doi.org/10.1101/294173

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