Title: Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis Hu J, Li H, Chooi YH Ref: Journal of the American Chemical Society, 141:8068, 2019 : PubMed
Paecilomyces variotii produces the antibacterial and cytotoxic ( M)-viriditoxin (1) together with a trace amount of its atropisomer ( P)-viriditoxin 1'. Elucidation of the biosynthesis by heterologous pathway reconstruction in Aspergillus nidulans identified the multicopper oxidase (MCO) VdtB responsible for the regioselective 6,6'-coupling of semiviriditoxin (10), which yielded 1 and 1' at a ratio of 1:2. We further uncovered that VdtD, an alpha/beta hydrolase-like protein lacking the catalytic serine, directs the axial chirality of the products. Using recombinant VdtB and VdtD as cell-free extracts from A. nidulans, we demonstrated that VdtD acts like a dirigent protein to control the stereoselectivity of the coupling catalyzed by VdtB to yield 1 and 1' at a ratio of 20:1. Furthermore, we uncovered a unique Baeyer-Villiger monooxygenase (BVMO) VdtE that could transform the alkyl methylketone side chain to methyl ester against the migratory aptitude.
Hu J, Li H, Chooi YH (2019) Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis Journal of the American Chemical Society141: 8068-8072
Hu J, Li H, Chooi YH (2019) Journal of the American Chemical Society141: 8068-8072