Cytochrome P450 induced formation of hydroxylated polybrominated diphenyl ether and dibenzo-p-dioxin derivates from brominated phenols

Methoxylated polybrominated diphenyl ethers (MeO-BDEs) are a class of environmentally relevant halogenated natural products. The two most relevant isomers, 2'-MeO-BDE 68 and 6-MeO-BDE 47, were repeatedly detected at levels comparable with persistent organic pollutants in marine environmental and food samples. MeO-BDEs were suspected to be biosynthesized by bromoperoxidases through the merging of two bromophenol units, three of which (2,4-dibromophenol, 2,6-dibromophenol and 2,4,6-tribromophenol) are abundant in marine environments, followed by O-methylation to give MeO-BDEs. However, not all abundant MeO-BDEs can be explained by the direct coupling of bromophenols. Therefore, several bromophenols were incubated with CYP109B1 from Bacillus subtilis. Incubations of 2,4-dibromophenol with CYP109B1 resulted in both 2'-OH-BDE 68 and 6-OH-BDE 47. Mechanistic considerations indicated that both compounds emerged from an epoxidized intermediate. After subsequent methylation this leads to the two most relevant MeO-BDEs in marine environments. By contrast, incubations with 2,6-dibromophenol and 2,4,6-tribromophenol did not form any OH-BDEs but tri- or tetrabrominated dibenzo-p-dioxins (PBDDs), i.e. another known class of environmentally relevant halogenated natural products whose toxicity has shown to be similar to their chlorinated analogues. SYNOPSIS: Treatment of bromophenols with cytochrome P450 monooxygenase CYP109B1 led to the formation of hydroxylated polybrominated diphenyl ethers and polybrominated dibenzo-p-dioxins.