open access

https://hdl.handle.net/2115/87824

Identification of Cyclopropane Formation in the Biosyntheses of Hormaomycins and Belactosins : Sequential Nitration and Cyclopropanation by Metalloenzymes

英語

Peptides

2022-02-07

Wiley-Blackwell

Angewandte chemie-international edition

61(7)

e202113189

Hormaomycins and belactosins are peptide natural products that contain unusual cyclopropane moieties. Bioinformatics analysis of the corresponding biosynthetic gene clusters showed that two conserved genes, hrmI/belK and hrmJ/belL, were potential candidates for catalyzing cyclopropanation. Using in vivo and in vitro assays, the functions of HrmI/BelK and HrmJ/BelL were established. HrmI and BelK, which are heme oxygenase-like dinuclear iron enzymes, catalyze oxidation of the epsilon-amino group of l-lysine to afford l-6-nitronorleucine. Subsequently, HrmJ and BelL, which are iron- and alpha-ketoglutarate-dependent oxygenases, effectively convert l-6-nitronorleucine into 3-(trans-2-nitrocyclopropyl)-alanine through C4-C6 bond installation. These observations disclose a novel pathway of cyclopropane ring construction and exemplify the new chemistry involving metalloenzymes in natural product biosynthesis.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: X. Li, R. Shimaya, T. Dairi, W.-c. Chang, Y. Ogasawara, Angew. Chem. Int. Ed. 2022, 61, e202113189., which has been published in final form at https://doi.org/10.1002/anie.202113189. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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