CmlI is an N-oxygenase in the biosynthesis of chloramphenicol

Tetrahedron
Haige LuHuimin Zhao

Abstract

The N-oxygenation of an amine group is one of the steps in the biosynthesis of the antibiotic chloramphenicol. The non-heme di-iron enzyme CmlI was identified as the enzyme catalyzing this reaction through bioinformatics studies and reconstitution of enzymatic activity. In vitro reconstitution was achieved using phenazine methosulfate and NADH as electron mediators, while in vivo activity was demonstrated in Escherichia coli using two substrates. Kinetic analysis showed a biphasic behavior of the enzyme. Oxidized hydroxylamine and nitroso compounds in the reaction were detected both in vitro and in vivo based on LC-MS. The active site metal was confirmed to be iron based on a ferrozine assay. These findings provide new insights into the biosynthesis of chloramphenicol and could lead to further development of CmlI as a useful biocatalyst.

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Citations

Jun 30, 2014·Bioorganic & Medicinal Chemistry·Emmanuel ChancoHuimin Zhao
Jan 8, 2015·Journal of the American Chemical Society·Thomas M MakrisJohn D Lipscomb
Jan 25, 2014·Chembiochem : a European Journal of Chemical Biology·Anna JirošováRobert Hanus
May 21, 2016·Journal of the American Chemical Society·Anna J KomorJohn D Lipscomb
May 28, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Cory J KnootJohn D Lipscomb
Jul 5, 2017·Journal of the American Chemical Society·Andrew J JasniewskiLawrence Que
Mar 20, 2018·Natural Product Reports·Anna J KomorJohn D Lipscomb
Oct 1, 2014·Antimicrobial Agents and Chemotherapy·Lorena T Fernández-MartínezMervyn J Bibb
Jun 25, 2019·Angewandte Chemie·Jason B Hedges, Katherine S Ryan
Jan 20, 2016·The Journal of General and Applied Microbiology·Karl J IndestDawn E Hancock
Oct 9, 2019·Nature Communications·Yuan-Yang GuoYong-Quan Li
Dec 30, 2020·Journal of Biotechnology·Matías L NóbileElizabeth S Lewkowicz
Apr 14, 2020·Materials Science & Engineering. C, Materials for Biological Applications·Libo ZhangQian Wang
Feb 18, 2020·Journal of the American Chemical Society·Effie C KisgeropoulosHannah S Shafaat
Mar 16, 2021·ACS Chemical Biology·Linyue ChenChangming Zhao
Mar 31, 2021·Nature Chemistry·Hai-Yan He, Katherine S Ryan
Apr 5, 2017·Chemical Reviews·Abraham J WaldmanEmily P Balskus
May 27, 2020·Organic Letters·Michael G KallitsakisIoannis N Lykakis

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