Natural Sources and Microbial Transformation of Marine Halogenated Pollutants

项目总结/摘要 天然多溴化有机化合物，如羟基化多溴联苯醚（OH--）， 溴化二苯醚和多溴化吡咯最近已成为引起人类健康关注的化学品。 这些人为卤代持久性有机污染物的天然产物亲属是 广泛分布于整个海洋食物网，并在人类食用的海产食品中积累。 我们和其他人已经证明，诸如6-OH-BDE-47（甲状腺激素受体）等OH-BDE 和PBPs，如四溴吡咯（兰尼碱受体）是强效毒素，因此对人体构成潜在风险 人类然而，关于这些自然资源的来源范围， 有机溴分子，这些化学物质如何进入并通过海洋食物网移动， 气候变化将影响其生产和积累，以及人类是否更多或更少 受天然卤代持久性有机污染物的影响，与它们的anthopogenic对应物。最近的发现， 摩尔和艾伦实验室已经严格建立了微生物的遗传和生化基础， 海洋细菌不同谱系中天然OH-BDE分子的合成。但全球 这些多溴持久性有机污染物在海洋生物群中的分布和普遍存在， 目前发现的来源，表明存在其他生物来源，并积极促进OH- - BDE和MeO--BDE在海洋食物网中的累积。这些信息对于更准确地 查明导致多溴二苯醚在海洋鱼类中自然积累的营养联系和相互转化， 最终，人类饮食暴露风险。在这个项目中，新的遗传和生化证据表明， 多溴联苯醚分子的生物合成和生物转化将建立海洋大型藻类， 使用转录组分析，海洋生境中多溴二苯醚分子的明显但未定性的来源 再加上生化酶的特性。多溴二苯醚的其他微生物来源 综合分析鱼类和海洋哺乳动物， 相关的微生物组使用整合的基因组和代谢组学方法结合实验 微生物组富集反应器中添加多溴二苯醚分子或生物合成基质。拟议 这项工作将由SIO的摩尔实验室（生物化学）和艾伦实验室（基因组学）联合进行， 在这些领域有良好的合作和联合指导记录。

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.