Characterization of the Aminocoumarin Ligase SimL from the Simocyclinone Pathway and Tandem Incubation with NovM,P,N from the Novobiocin Pathway
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- 作者：Michelle Pacholec ; Caren L. Freel Meyers ; Markus Oberthü ; r ; Daniel Kahne ; and Christopher T. Walsh
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：March 29, 2005
- 年：2005
- 卷：44
- 期：12
- 页码：4949 - 4956
- 全文大小：134K
- 年卷期：v.44,no.12(March 29, 2005)
- ISSN：1520-4995
文摘
Simocyclinone D8 consists of an anguicycline C-glycoside tethered by a tetraene diester linkerto an aminocoumarin. Unlike the antibiotics novobiocin, clorobiocin, and coumermycin A1, the phenolichydroxyl group of the aminocoumarin in simocyclinone is not glycosylated with a decorated noviosylmoiety that is the pharmacophore for targeting bacterial DNA gyrase. We have expressed the Streptomycesantibioticus simocyclinone ligase SimL, purified it from Escherichia coli, and established its ATP-dependentamide bond forming activity with a variety of polyenoic acids including retinoic acid and fumagillin. Wehave then used the last three enzymes from the novobiocin pathway, NovM, NovP, and NovN, to converta SimL product to a novel novobiocin analogue, in which the 3-prenyl-4-hydroxybenzoate of novobiocinis replaced with a tetraenoate moiety, to evaluate antibacterial activity.