Evolving proteins with improved solubility

Wang, T. et al. Nat. Chem. Biol. 14, 972–980 (2018).

Escherichia coli is the most widely used organism for recombinant protein expression, but the majority of nonbacterial proteins cannot be expressed in this bug in soluble form. Directed evolution is a promising approach for generating protein variants with a desired function that also have improved solubility, as demonstrated recently by Wang et al. Using their previously established phage display-based PACE (phage-assisted continuous evolution) system, the researchers additionally implemented the use of a split-intein minor coat protein III—which is required for the generation of infectious progeny phage—to enable two concurrent positive selections. This approach allows them to select for both function and improved solubility. They applied this soluble expression (SE)-PACE method to evolve antibody fragments with improved expression in just a few days, as well as to generate APOBEC1 cytidine deaminase variants with improved solubility and base-editing activity.

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Correspondence to Allison Doerr.

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Doerr, A. Evolving proteins with improved solubility. Nat Methods 15, 763 (2018).

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