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Issue 7, 2017
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Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification

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Abstract

Flavoenzymes are ubiquitous in biological systems and catalyze a diverse range of chemical transformations. The flavoenzyme XiaK from the biosynthetic pathway of the indolosesquiterpene xiamycin A is demonstrated to mediate the in vivo biotransformation of xiamycin A into multiple products, including a chlorinated adduct as well as dimers characterized by C–N and N–N linkages that are hypothesized to form via radical-based mechanisms. Isolation and characterization of XiaK in vitro shows that it acts as a flavin-dependent N-hydroxylase that catalyzes the hydroxylation of xiamycin A at the carbazole nitrogen to form N-hydroxyxiamycin, a product which was overlooked in earlier in vivo experiments because its chemical and chromatographic properties are similar to those of oxiamycin. N-Hydroxyxiamycin is shown to be unstable under aerobic conditions, and characterization by electron paramagnetic resonance spectroscopy demonstrates formation of an N-hydroxycarbazole radical adduct. This radical species is proposed to serve as a key intermediate leading to the formation of the multiple xiamycin A adducts. This study suggests that non-enzyme catalyzed reactions may play a greater role in the biosynthesis of natural products than has been previously recognized.

Graphical abstract: Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification

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Publication details

The article was received on 15 Mar 2017, accepted on 27 Apr 2017 and first published on 04 May 2017


Article type: Edge Article
DOI: 10.1039/C7SC01182B
Citation: Chem. Sci., 2017,8, 5067-5077
  • Open access: Creative Commons BY-NC license
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    Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification

    Q. Zhang, H. Li, L. Yu, Y. Sun, Y. Zhu, H. Zhu, L. Zhang, S. Li, Y. Shen, C. Tian, A. Li, H. Liu and C. Zhang, Chem. Sci., 2017, 8, 5067
    DOI: 10.1039/C7SC01182B

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