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Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
The same but different: multiple functions of the fungal flavin dependent monooxygenase SorD from Penicillium
Lukas Kahlert1, Russell J Cox, Elizabeth Skellam
1Institute for Organic Chemistry and BMWZ Leibniz University of Hannover Schneiderberg 38, 30167, Hannover, Germany. elizabeth.skellam@oci.uni-hannover.de.
Abstract:
Sorbicillinoids are a large family of fungal secondary metabolites with a diverse range of structures and numerous bioactivites, some of which have pharmaceutical potential. The flavin-dependent monooxygenase SorD from Penicillium chrysogenum (PcSorD) utilizes sorbicillinol to catalyze a broad scope of reactions: formation of oxosorbicillinol and epoxysorbicillinol; intermolecular Diels-Alder and Michael-addition dimerization reactions; and dimerization of a sorbicillinol derivative with oxosorbicillinol. PcSorD shares only 18.3% sequence identity with SorD from Trichoderma reesei (TrSorD) and yet unexpectedly catalyzes many of the same reactions, however, the formation of oxosorbicillinol and bisvertinolone by PcSorD extends the range of reactions catalyzed by a single enzyme. Phylogenetic analysis indicates that PcSorD and TrSorD bind the flavin cofactor covalently but via different residues and point mutations confirm these residues are essential for activity.
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