Molecular insights into the endoperoxide formation by Fe(II)/α-KG-dependent oxygenase NvfI

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Original languageEnglish
Article number4417
Journal / PublicationNature Communications
Volume12
Online published20 Jul 2021
Publication statusPublished - 2021

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Abstract

Endoperoxide-containing natural products are a group of compounds with structurally unique cyclized peroxide moieties. Although numerous endoperoxide-containing compounds have been isolated, the biosynthesis of the endoperoxides remains unclear. NvfI from Aspergillus novofumigatus IBT 16806 is an endoperoxidase that catalyzes the formation of fumigatonoid A in the biosynthesis of novofumigatonin. Here, we describe our structural and functional analyses of NvfI. The structural elucidation and mutagenesis studies indicate that NvfI does not utilize a tyrosyl radical in the reaction, in contrast to other characterized endoperoxidases. Further, the crystallographic analysis reveals significant conformational changes of two loops upon substrate binding, which suggests a dynamic movement of active site during the catalytic cycle. As a result, NvfI installs three oxygen atoms onto a substrate in a single enzyme turnover. Based on these results, we propose a mechanism for the NvfI-catalyzed, unique endoperoxide formation reaction to produce fumigatonoid A.

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Molecular insights into the endoperoxide formation by Fe(II)/α-KG-dependent oxygenase NvfI. / Mori, Takahiro; Zhai, Rui; Ushimaru, Richiro et al.
In: Nature Communications, Vol. 12, 4417, 2021.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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