Assembly of Dimeric Variants of Coumermycins by Tandem Action of the Four Biosynthetic Enzymes CouL, CouM, CouP, and NovN

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• 作者：Caren L. Freel Meyers ; Markus Oberth&uuml ; r ; Lutz Heide ; Daniel Kahne ; and Christopher T. Walsh
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：November 30, 2004
• 年：2004
• 卷：43
• 期：47
• 页码：15022 - 15036
• 全文大小：783K
• 年卷期：v.43,no.47(November 30, 2004)
• ISSN：1520-4995

文摘

Coumermycin A₁ is a member of the aminocoumarin family of antibiotics. Unlike its structuralrelatives, novobiocin and clorobiocin, coumermycin A₁ is a dimer built on a 3-methyl-2,4-dicarboxypyrrolescaffold and bears two decorated noviose sugar components which are the putative target binding motifsfor DNA gyrase. Starting with this scaffold, we have utilized the ligase CouL for mono- and bisamideformation with aminocoumarins to provide substrates for the glycosyltransferase CouM. CouM wassubsequently shown to catalyze mono- and bisnoviosylation of the resulting CouL products. CouP wasshown to possess 4'-O-methyltransferase activity on products from tandem CouL, CouM assays. A fourthenzyme, NovN, the 3'-O-carbamoyltransferase from the novobiocin operon, was then able to carbamoylateeither or both arms of the CouP product. The tandem action of CouL, CouM, CouP, and NovN thusgenerates a biscarbamoyl analogue of the pseudodimer coumermycin A₁. Starting from alternative dicarboxyscaffolds, these four enzymes can be utilized in tandem to create additional variants of dimericaminocoumarin antibiotics.