N. Tokuriki

This study shows that epistasis in enzyme evolution arises from shifting the rate-limiting step in the catalytic cycle, leading to substantial activity enhancements through synergistic mutations.

The paper shows neutral drift and threshold selection generate phenotypic variation in antibiotic resistance genes without adaptation.

This study shows that higher-order epistasis causes idiosyncrasy in protein evolution, making predictions unreliable even with epistatic information.

This study quantifies functional heterogeneity in wild-type and mutant alkaline phosphatase, finding that genetic perturbations increase heterogeneity and correlate with promiscuous activities.

The paper constructs an empirical phenotype-fitness landscape for VIM-2 β-lactamase across ampicillin concentrations, showing environmental dependence of mutational effects and nonspecific epistasis.

This paper identifies mechanisms of niclosamide action and resistance in Gram-negative bacteria and demonstrates synergistic combination therapies with efflux inhibitors and membrane permeabilizers.

This study uses deep mutational scanning to analyze VIM-2 lactamase variants, identifying residues affecting stability, translocation, and substrate specificity across different temperatures.

The paper shows that secondary environmental factors influence the evolutionary adaptation of an enzyme by shifting the adaptive landscape and altering fitness peaks.

This study introduces TRIAD, a transposon mutagenesis method to generate InDels for directed enzyme evolution, showing distinct functional outcomes compared to point mutagenesis.

This paper investigates hidden phenotypic variation in metallo-β-lactamase (MBL) orthologs across different hosts, finding that resistance levels depend on both catalytic efficiency and periplasmic enzyme abundance.