Biosynthesis of diazepinomicin/ECO-4601, a Micromonospora secondary metabolite with a novel ring system

Journal of Natural Products
James B McAlpineGuy T Carter

Abstract

The novel microbial metabolite diazepinomicin/ECO-4601 (1) has a unique tricyclic dibenzodiazepinone core, which was unprecedented among microbial metabolites. Labeled feeding experiments indicated that the carbocyclic ring and the ring nitrogen of tryptophan could be incorporated via degradation to the 3-hydroxyanthranilic acid, forming ring A and the nonamide nitrogen of 1. Genomic analysis of the biosynthetic locus indicated that the farnesyl side chain was mevalonate derived, the 3-hydroxyanthranilic acid moiety could be formed directly from chorismate, and the third ring was constructed via 3-amino-5-hydroxybenzoic acid. Successful incorporation of 4,6-D2-3-hydroxyanthranilic acid into ring A of 1 via feeding experiments supports the genetic analysis and the allocation of the locus to this biosynthesis. These studies highlight the enzymatic complexity needed to produce this structural type, which is rare in nature.

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Citations

Mar 17, 2010·Biochemistry·Brian D Ames, Christopher T Walsh
Aug 16, 2011·Journal of the American Chemical Society·Dmitry Tsvelikhovsky, Stephen L Buchwald
Oct 22, 2009·Natural Product Reports·Markus NettBradley S Moore
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Oct 22, 2013·Journal of Industrial Microbiology & Biotechnology·Caitlin D Deane, Douglas A Mitchell
Jan 9, 2010·Bioorganic & Medicinal Chemistry Letters·Satoshi MiyanagaYasuhiro Igarashi
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Feb 27, 2020·Chemistry & Biodiversity·Sisi QiPeng Sun
May 28, 2019·Frontiers in Microbiology·Jessica Thandara GosseChristopher N Boddy
Nov 11, 2020·Natural Product Reports·Jeffrey D RudolfZining Li
Feb 10, 2009·Journal of Natural Products·Anokha S RatnayakeGuy T Carter
Jan 21, 2010·Journal of Natural Products·Miho IzumikawaKazuo Shin-ya
Aug 16, 2018·Journal of Natural Products·Jana BraeselAlessandra S Eustáquio
Mar 22, 2019·Journal of Natural Products·Jana BraeselAlessandra S Eustáquio
Sep 6, 2011·European Journal of Medicinal Chemistry·Bhuwan B Mishra, Vinod K Tiwari

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