Natural polybrominated organic compounds such as hydroxylated polybrominated diphenyl ethers (OH- BDEs)andpolybrominatedpyrroles(PBPs)haverecentlyemergedaschemicalsofhumanhealthconcern. These natural product relatives of anthropogenic halogenated persistent organic pollutants (POPs) are widely distributed throughout the marine food web and accumulate in seafood sources consumed by humans. We and others have demonstrated that OH-BDEs such as 6-OH-BDE-47 (thyroid hormone receptor) and PBPs such as tetrabromopyrrole (ryanodine receptor) are potent toxins and thus pose a potential risk to humans. Many fundamental questions however remain about the extent of sources for these natural organobromine molecules, how these chemicals enter and move through the marine food web,whetherchangesintheclimatewillimpacttheirproductionandaccumulation,andwhetherhumans aremoreorlessimpactedbynaturalhalogenatedPOPsversustheiranthopogenticcounterparts.Recent discoveriesbytheMooreandAllenlaboratorieshaverigorouslyestablishedthegeneticandbiochemical basis for the microbial synthesis of natural OH-BDE molecules in diverse lineages of marine bacteria. However,theglobaldistributionandubiquityofthesepolybrominatedPOPsinmarinebiotacannotbefully explainedbythesourcesdiscoveredthusfar,suggestingadditionalbiogenicsourcesexistandareactively contributingtoOH-BDEandMeO-BDEaccumulationinthemarinefoodweb.Thisinformationiscriticalto moreaccuratelyidentifytrophicconnectionsandinterconversionsthatleadtonaturalPBDEaccumulation inmarinefishandultimately,humandietaryexposurerisks.Inthisproject,newgeneticandbiochemical evidence for the biosynthesis and biotransformation of PBDE molecules will be established for marine macroalgae, a conspicuous but uncharacterized source of PBDE molecules in marine habitats, using transcriptomeanalysiscoupledwithbiochemicalenzymecharacterization.Additionalmicrobialsourcesfor PBDE synthesis/transformation will be characterized by the comprehensive analysis of fish and marine- mammalassociatedmicrobiomesusingintegratedgenomicandmetabolomicapproachescombinedwith experimentalmicrobiomeenrichmentreactorsamendedwithPBDEmoleculesorbiosyntheticsubstrates. The proposed work will be undertaken jointly by the laboratories of Moore (biochemistry) and Allen (genomics)atSIOwhohaveaproventrackrecordofcollaborationandjointmentorshipintheseareas.
PublicHealthRelevanceStatement Polyhalogenated aromatic chemicals like polybrominated diphenyl ether (PBDE) fire retardants have been restricted from commercial use due to their environmental bioaccumulation and human toxicity. Remarkably, marine microbes also naturally biosynthesize PBDE molecules. ThiscollaborativeprojectwilldiscoverandcharacterizenewroutesofPBDEbiosynthesisinthe marineenvironment,includingfishandothermarinefoodsconsumedbyhumans.
