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

The ATP-dependent amide bond forming activity of Streptomyces antibioticus simocyclinone ligase SimL was expressed and purified from Escherichia coli with a variety of polyenoic acids including retinoic acid and fumagillin. The last three enzymes from the novobiocin pathway, namely, NovM, NovP, and NovN, are used to convert a SimL product to a novel novobiocin analogue, in which the 3-prenyl-4-hydroxybenzoate of novobiocin is replaced with a tetranoate moiety.