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Updated: Sep 19, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals
Published on: April 19, 2019
Intermolecular Carbon-Carbon Naphthalene Coupling Involves a Radical Mechanism Driven by Cytochrome P450 in
Jia Gao1, Leyao Chen2, Karin Steffen3,4
1Dept. of Microbiology, Institute for Applied Biosciences, Karlsruhe Institute of Technology (KIT) - South Campus, Karlsruhe, Germany.
Abstract:
Dihydroxynaphthalene (DHN) derivatives are precursors of biologically important molecules, including melanin and perylenequinones (PQs). Biosynthesis of DHN-derived metabolites requires precise spatial control of radical reactions to form specific C─C or C─O─C bonds. Investigating fungal PQ biosynthesis in Alternaria alternata, we identified a cytochrome P450 enzyme that catalyzes a highly regio- and stereospecific C─C radical coupling reaction. Conversely, a DHN-converting P450 from Berkleasmium sp. utilizes a diradical mechanism yielding a C─O─C bridge. Comparing these enzymes revealed five sequence motifs that, with structural modeling, allowed the identification of a novel A. alternata enzyme converting 1,8-DHN to a 2-2' DHN dimer. We demonstrate that P450-dependent PQ biosynthesis in A. alternata is fundamentally distinct from the laccase-fasciclin-mediated pathway in Cercospora beticola, indicating that PQ biosynthesis evolved via distinct, lineage-specific pathways through convergent evolution. Finally, PQs contribute to microbial niche shaping on tomato fruits. Understanding these pathways provides a foundation for producing PQs for medical applications.
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