N. Tokuriki

Understanding epistatic networks in the B1 -lactamases through coevolutionary statistical modeling and deep mutational scanning

The paper uses coevolutionary analysis and deep mutational scanning to study epistatic networks in B1-lactamases, revealing both conserved and specific interactions across homologs.

Origin Of Evolutionary Bifurcation In An Enzyme

The paper describes how two distinct enzymes evolved from a common ancestor through different mutational paths, leading to divergent molecular and phenotypic outcomes.

Epistasis Arises from Shifting the Rate-Limiting Step during Enzyme Evolution

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.

Neutral Drift and Threshold Selection Promote Phenotypic Variation

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

Higher-order epistasis creates idiosyncrasy, confounding predictions in protein evolution

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

Genetic perturbation enhances functional heterogeneity in alkaline phosphatase

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

Environmental selection and epistasis in an empirical phenotype-environment-fitness landscape

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.

Mechanistic understanding enables the rational design of salicylanilide combination therapies for Gram-negative infections

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

Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase.

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

Secondary environmental variation creates a shifting evolutionary watershed for the methyl- parathion hydrolase enzyme

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

Access to unexplored regions of sequence space in directed enzyme evolution via insertion/deletion mutagenesis

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

The molecular mechanisms underlying hidden phenotypic variation among metallo-β-lactamases

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.

Higher-order epistatic networks underlie the evolutionary fitness landscape of a xenobiotic- degrading enzyme

This study identifies five mutations that enable the evolution of a xenobiotic-degrading enzyme and shows that higher-order epistasis shapes its adaptive landscape and substrate specificity.