Characterization of the aminocoumarin ligase SimL from the simocyclinone pathway and tandem incubation with NovM,P,N from the novobiocin pathway

Michelle Pacholec, Caren L Meyers, Markus Oberthür, Daniel Kahne, Christopher T. Walsh

Research output: Contribution to journalArticle

Abstract

Simocyclinone D8 consists of an anguicycline C-glycoside tethered by a tetraene diester linker to an aminocoumarin. Unlike the antibiotics novobiocin, clorobiocin, and coumermycin A1, the phenolic hydroxyl group of the aminocoumarin in simocyclinone is not glycosylated with a decorated noviosyl moiety that is the pharmacophore for targeting bacterial DNA gyrase. We have expressed the Streptomyces antibioticus simocyclinone ligase SimL, purified it from Escherichia coli, and established its ATP-dependent amide bond forming activity with a variety of polyenoic acids including retinoic acid and fumagillin. We have then used the last three enzymes from the novobiocin pathway, NovM, NovP, and NovN, to convert a SimL product to a novel novobiocin analogue, in which the 3-prenyl-4-hydroxybenzoate of novobiocin is replaced with a tetraenoate moiety, to evaluate antibacterial activity.

Original languageEnglish (US)
Pages (from-to)4949-4956
Number of pages8
JournalBiochemistry®
Volume44
Issue number12
DOIs
StatePublished - Mar 29 2005
Externally publishedYes

Fingerprint

Aminocoumarins
Novobiocin
Ligases
Streptomyces antibioticus
DNA Gyrase
Bacterial DNA
Tretinoin
Amides
Hydroxyl Radical
Escherichia coli
Adenosine Triphosphate
Anti-Bacterial Agents
Acids
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of the aminocoumarin ligase SimL from the simocyclinone pathway and tandem incubation with NovM,P,N from the novobiocin pathway. / Pacholec, Michelle; Meyers, Caren L; Oberthür, Markus; Kahne, Daniel; Walsh, Christopher T.

In: Biochemistry®, Vol. 44, No. 12, 29.03.2005, p. 4949-4956.

Research output: Contribution to journalArticle

Pacholec, Michelle ; Meyers, Caren L ; Oberthür, Markus ; Kahne, Daniel ; Walsh, Christopher T. / Characterization of the aminocoumarin ligase SimL from the simocyclinone pathway and tandem incubation with NovM,P,N from the novobiocin pathway. In: Biochemistry®. 2005 ; Vol. 44, No. 12. pp. 4949-4956.
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