title: Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027.
abstract: The C-1027 enediyne antitumor antibiotic from Streptomyces globisporus possesses an (S)-3-chloro-5-hydroxy-beta-tyrosine moiety, the chloro- and hydroxy-substituents of which are installed by a flavin-dependent halogenase SgcC3 and monooxygenase SgcC, respectively. Interestingly, a single flavin reductase, SgcE6, can provide reduced flavin to both enzymes. Bioinformatics analysis reveals that, similar to other flavin reductases involved in natural product biosynthesis, SgcE6 belongs to the HpaC-like subfamily of the Class I flavin reductases. The present study describes the steady-state kinetic characterization of SgcE6 as a strictly NADH- and FAD-specific enzyme.
authors.affiliation: Division of Pharmaceutical Sciences, University of Wisconsin-Madison, 777 Highland Avemue, Madison, WI 53705, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Van Lanen
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Horsman
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D016000:Cluster Analysis; D053281:Enediynes / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D054879:Halogenation; D006900:Hydroxylation; D007700:Kinetics; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017385:Sequence Homology; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D053281:Enediynes; D009243:NAD; C058024:C 1027; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases