Bacterial cytochrome P450 for oxidative halogenated biaryl coupling.

Area of Science:

• Biocatalysis and enzyme engineering
• Organic synthesis and medicinal chemistry

Background:

• Biaryl motifs are crucial in pharmaceuticals, agrochemicals, and materials.
• Traditional biaryl synthesis methods are often inefficient and unsustainable.
• Biocatalytic approaches for halogenated biaryl coupling are underdeveloped.

Purpose of the Study:

• To functionally characterize the marine-derived cytochrome P450 enzyme Bmp7.
• To explore Bmp7's capability in catalyzing halogenated biaryl formation.
• To elucidate the mechanism of Bmp7-catalyzed coupling reactions.

Main Methods:

• Recombinant expression and characterization of Bmp7.
• Substrate screening using a library of halogenated phenols.
• Product identification via LC-HRMS, HRMS/MS, GC-MS, and NMR.
• Structural analysis using X-ray crystallography and DFT calculations.

Main Results:

• Bmp7 efficiently catalyzes C-C homocoupling of halogenated phenols, forming ortho-ortho linked biaryls.
• Bmp7 accepts a broad range of 17 halogenated phenols as substrates.
• Bmp7 also mediates heterocoupling reactions, producing mixed biaryl products.
• X-ray crystallography and DFT calculations suggest a single-radical mechanism.

Conclusions:

• Bmp7 is a novel biocatalyst for synthesizing halogenated biaryls.
• This study provides a foundation for enzyme engineering and biocatalytic applications.
• Bmp7 offers a sustainable alternative to traditional biaryl synthesis methods.