Nobuhiko Tokuriki

The global β-lactam resistome revealed by comprehensive sequence analysis

The paper maps the global distribution of β-lactamases across environments and microbes, revealing their abundance and potential origins in plant and wastewater ecosystems.

Substrate-dependent epistasis probes active site intramolecular wiring

This study maps substrate-dependent epistasis in phosphotriesterase by analyzing 64 mutation combinations across nine substrates, revealing how intramolecular wiring changes to support promiscuity and functional trade-offs.

Single-Molecule Kinetic Exploration of Functional Substates in an Evolving Phosphotriesterase

This study investigates how functional and conformational substates change during enzyme evolution using single-molecule kinetic assays and simulations, showing coordinated shifts in substate equilibria that optimize catalytic efficiency.

Free energy perturbations in enzyme kinetic models reveal cryptic epistasis

This paper shows enzyme kinetic parameters exhibit non-specific epistasis due to multi-state catalytic cycles, and provides tools to correct for this effect in mechanistic inference.

Evolution tunes functional sub-state interconversion to boost enzyme function

This paper shows how evolution improves enzyme function by shifting the rate-limiting step from substrate binding to sub-state interconversion in β-lactamase OXA-48.

Stability of multi-species consortia during microbial metabolic evolution

This study shows that ecological matching between metabolic roles and nutrient strategies stabilizes multi-species consortia during microbial metabolic evolution.

Exploring large protein sequence space through homology- and representation-based hierarchical clustering

The paper introduces a sequence analysis pipeline that improves exploration of protein sequence space through hierarchical clustering and alternative homology metrics, demonstrating scalability and utility in analyzing large datasets.

Widespread promiscuous alkaline phosphatases underscore early microbial phosphite utilization

The paper identifies alkaline phosphatase (AP) as a widespread promiscuous enzyme capable of oxidizing phosphite, contributing to microbial phosphorus cycling.

The temperature dependence of binding entropy is a selective pressure in protein evolution

The paper examines how thermodynamic binding strategies in proteins evolved in response to temperature changes, showing a shift from entropy-driven to enthalpy-driven binding over time.

Leveraging ancestral sequence reconstruction for protein representation learning

This paper introduces LASE, a method using ancestral sequence reconstruction to train protein language models with higher accuracy and faster computation than large models.

Evolution of β-lactamase mediated cefiderocol resistance

This study shows that β-lactamases from different Ambler classes confer cefiderocol resistance and can evolve to increase resistance through mutations.

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.

A revised biosynthetic pathway for the cofactor F420 in bacteria

The paper revises the biosynthetic pathway for the cofactor F420 in bacteria by identifying the correct substrate for guanylyltransferases and elucidating the role of the C-terminal domain of FbiB.

Evolution of an enzyme from a solute-binding protein

This study shows how an enzyme evolved from a solute-binding protein through structural and catalytic changes, highlighting mechanisms of de novo enzyme emergence.