9YVV

Cocrystallized structure of Bmp7 in complex with 2,4-dibromophenol

Summary for 9YVV

• Entry DOI: 10.2210/pdb9yvv/pdb
• Descriptor: Polybrominated aromatic compounds synthase, GLYCEROL, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: cytochrome p450 enzyme, biaryl coupling, oxidoreductase
• Biological source: Marinomonas mediterranea
• Total number of polymer chains: 1
• Total formula weight: 57918.45

Authors

Nolan, K.,Wang, Y. (deposition date: 2025-10-23, release date: 2026-01-07, Last modification date: 2026-03-18)

Primary citation

Petriti, V.,Nolan, K.,Xu, W.,Tsai, S.,Wang, X.,Xie, W.J.,Zheng, G.,Wang, Y.,Ding, Y.
Bacterial cytochrome P450 for oxidative halogenated biaryl coupling.
Acs Catalysis, 16:2615-2627, 2026

PubMed Abstract: Biaryl motifs are fundamental structural elements in many pharmaceuticals, agrochemicals, and advanced materials. Traditional synthetic approaches for biaryl bond formation often require harsh conditions, costly catalysts, and pre-functionalized starting materials, which limit their efficiency, sustainability, and substrate scope. Enzymatic catalysis offers a greener alternative. However, biocatalysts capable of directly coupling halogenated biaryl compounds remain largely underexplored. Here, we report the functional characterization of the marine-derived cytochrome P450 enzyme Bmp7, which catalyzes the formation of halogenated biaryls. We first characterized the product profile of recombinant Bmp7 using its native substrate 2,4-dibromophenol () and confirmed the dominant - C-C homocoupled product as MC21-A. Screening a halogenated aromatic substrate library revealed that Bmp7 binds and catalyzes the coupling of 17 halogenated phenols, as evidenced by spectral shift assays, LC-HRMS, HRMS/MS and GC-MS analyses. Two homocoupled products were structurally confirmed by NMR analysis to possess C-C linkages. In addition to efficient homocoupling, Bmp7 catalyzed heterocoupling reactions between substrate and 16 other substrates, producing mixtures of homocoupled and heterocoupled halogenated biphenols. X-ray crystallography revealed the binding of two substrate molecules within the active site, while DFT calculations supported a single-radical reaction mechanism, shedding light on the mechanistic basis of the coupling reaction. Together, these findings lay the groundwork for these findings establish a foundation for future efforts in enzyme engineering and the development of biocatalytic strategies for synthetic applications.

PubMed: 41789186
DOI: 10.1021/acscatal.5c08060

Experimental method

X-RAY DIFFRACTION (2.32 Å)