Peng Liu

Designing enzymes for new-to-nature chemistry and non-natural substrates with AlphaProtein Novo

Design-Evolution Synergy Enables New-to-Nature Enzyme Chemistry

Directed evolution and machine-learning-assisted evolution have transformed biocatalysis by enabling rapid optimisation of catalytic performance within compatible protein scaffolds. In parallel, advances in deep-learning-driven de novo protein design have expanded accessible protein architectural space, enabling the ge...

Catalytic Redox-Neutral Decarboxylative Aromatization via Transfer Dehydrogenation

Arenes are fundamental structural motifs in organic molecules; therefore, methods for introducing aromatic rings are of broad importance. Traditional approaches that install arenes early followed by postfunctionalization sometimes struggle to achieve diverse substitution patterns, high chemoselectivity, or satisfacto...

A binuclear copper enzyme platform for enantioconvergent radical (pseudo)halogenation

Despite their intriguing native metalloenzymology, naturally occurring copper enzymes remain largely underexploited for new-to-nature biocatalytic reactions. Herein, we report the systematic investigation and reprogramming of natural copper enzymes to catalyze unnatural free radical (pseudo)halogenation reaction in a h...

Chiral oxazolidinones via biocatalytic aziridination of unactivated alkenes.

Directed Evolution of Nonheme Fe Enzymes for Enantioselective and Regiodivergent 1,3- and 1,4-Nitrogen Migration: Biocatalytic Asymmetric Synthesis of Noncanonical α- and β-Amino Acids.

Two complementary nitrogen migratases were developed that enabled biocatalyst-controlled 1,3- and 1,4-nitrogen migration with excellent regioselectivity and exhibited similar kinetic isotope effects for both 1,5- and 1,6-HAT pathways, suggesting that enzyme engineering controls regio- and enantioselectivity but does no...