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  • Diaryl Ether Formation by a...
    Wei, Qian; Wang, Ze-Ping; Zhang, Xiao; Zou, Yi

    Journal of the American Chemical Society, 06/2022, Volume: 144, Issue: 22
    Journal Article

    Oxidative coupling and oxidative rearrangement are two of the most common biosynthetic strategies to form diaryl ethers. In contrast, enzymatic diaryl ether generation that proceeds in a nonoxidative manner has not been characterized thus far. Here, we discovered a versatile thioesterase (TE) domain from the nonreducing polyketide synthase (nrPKS) AN7909, which catalyzes diaryl ether formation through a series of successive steps involving esterification, a Smiles rearrangement, and hydrolysis. Further mutations and biochemical analyses with synthetic mimic substrates provide insight into the proposed catalytic process of the TE domain.