Characterization of kinetics and products of the Baeyer-Villiger oxygenase MtmOIV, the key enzyme of the biosynthetic pathway toward the natural product anticancer drug mithramycin from Streptomyces argillaceus.
MtmOIV, the key oxygenase of the mithramycin biosynthetic pathway in Streptomyces argillaceus, was proven to act initially as Baeyer-Villiger monooxygenase, but may also catalyze various follow-up reaction steps. The reaction of the overexpressed pure His6-tagged enzyme with its substrate premithramycin B was studied. Various intermediates and products were isolated and physicochemically characterized, several of them being previously unknown compounds. This is the first example in which a bacterial enzyme was unequivocally proven to act as Baeyer-Villigerase with its natural substrate, that is, in its natural context.
Gibson
Miranda
M
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536-0082, USA.
Nur-e-alam
Mohammad
M
Lipata
Fredilyn
F
Oliveira
Marcos A
MA
Rohr
Jürgen
J
D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D007700:Kinetics; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008926:Plicamycin / Q000096:biosynthesis*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D010105:Oxygenases; D008926:Plicamycin