Project Summary/Abstract Natural polybrominated organic compounds such as hydroxylated polybrominated diphenyl ethers (OH- BDEs) and polybrominated pyrroles (PBPs) have recently emerged as chemicals of human health concern. 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, whether changes in the climate will impact their production and accumulation, and whether humans are more or less impacted by natural halogenated POPs versus their anthopogentic counterparts. Recent discoveries by the Moore and Allen laboratories have rigorously established the genetic and biochemical basis for the microbial synthesis of natural OH-BDE molecules in diverse lineages of marine bacteria. However, the global distribution and ubiquity of these polybrominated POPs in marine biota cannot be fully explained by the sources discovered thus far, suggesting additional biogenic sources exist and are actively contributing to OH-BDE and MeO-BDE accumulation in the marine food web. This information is critical to more accurately identify trophic connections and interconversions that lead to natural PBDE accumulation in marine fish and ultimately, human dietary exposure risks. In this project, new genetic and biochemical 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 transcriptome analysis coupled with biochemical enzyme characterization. Additional microbial sources for PBDE synthesis/transformation will be characterized by the comprehensive analysis of fish and marine- mammal associated microbiomes using integrated genomic and metabolomic approaches combined with experimental microbiome enrichment reactors amended with PBDE molecules or biosynthetic substrates. The proposed work will be undertaken jointly by the laboratories of Moore (biochemistry) and Allen (genomics) at SIO who have a proven track record of collaboration and joint mentorship in these areas.