| Abstract
| - Resistoflavin (1) is a rare boat-shaped pentacyclic polyketide metabolite of Streptomycesresistomycificus with marked antibacterial activity. By a series of experiments we have disclosed that theoptically active molecule is derived from the discoid polyketide resistomycin (2) by an unusual, enantioface-differentiating hydroxylation, which leads to the capped pentacyclic ring system. In vivo and in vitroexperiments unequivocally demonstrate that this reaction is catalyzed by RemO, an FAD-dependentmonooxygenase. In addition, we were able to establish the absolute configuration of 1 and thus thestereochemical course of this rare enzymatic reaction by extensive computational methods. Comparisonof the experimental CD spectrum with those quantum chemically calculated for (R)-1 and (S)-1 revealedthe R-configuration of 1. Consequently, the enzyme-catalyzed hydroxylation takes place from the Re-faceof 2 with loss of aromaticity in favor of a chiral carbinol center. While other oxygenases involved in polyketidetailoring functionalize the periphery of polyphenols, RemO is unique in its ability to catalyze a central,nonperipheral hydroxylation of a fused ring system.
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