Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027 |
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| Authors: | Steven G. Van Lanen,Shuangjun Lin,Geoff P. Horsman,& Ben Shen |
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| Affiliation: | Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, USA;;University of Wisconsin National Cooperative Drug Discovery Group, University of Wisconsin-Madison, Madison, WI, USA;;and Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA |
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| Abstract: | The C-1027 enediyne antitumor antibiotic from Streptomyces globisporus possesses an ( S )-3-chloro-5-hydroxy-β-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. |
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| Keywords: | C-1027 enediyne flavin reductase halogenase monooxygenase SgcE6 |
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