Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis

Jinyu Hu, Hang Li, Yit-Heng Chooi

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25 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)8068-8072
Number of pages5
JournalJournal of the American Chemical Society
Volume141
Issue number20
DOIs
Publication statusPublished - 2020

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