Engineered and Artificial Metalloenzymes for Selective C-H Functionalization

Area of Science:

• Organic Chemistry
• Biocatalysis
• Enzyme Engineering

Background:

• Direct C-H bond functionalization is crucial for organic synthesis but faces challenges in selectivity for complex molecules.
• Metalloenzymes provide a tunable platform for catalyst-controlled C-H bond functionalization through protein engineering and cofactor modification.

Purpose of the Study:

• To review recent advancements in engineered and artificial metalloenzymes for C-H functionalization.
• To highlight biocatalytic strategies for selective C-H oxyfunctionalization, halogenation, amination, and carbene insertion.

Main Methods:

• Focus on engineered heme- and non-heme iron-dependent enzymes.
• Exploration of abiological nitrene and carbene transfer chemistries.
• Protein engineering and cofactor redesign for tuning enzyme reactivity and selectivity.

Main Results:

• Engineered metalloenzymes demonstrate high chemo-, regio-, and stereocontrol in C-H functionalization.
• Tunable selectivity achieved through enzyme design and cofactor environment.
• Successful application in selective C-H oxyfunctionalization, halogenation, amination, and carbene insertion.

Conclusions:

• Engineered metalloenzymes represent a powerful and sustainable approach to organic synthesis.
• These biocatalytic systems expand synthetic toolboxes for generating chiral building blocks and late-stage functionalization.
• Opens new avenues for natural product total synthesis and complex molecule diversification.