Interrogating novel biosynthetic sources for the production of polybrominated diphenyl ethers

探究生产多溴二苯醚的新型生物合成来源

• 批准号: 10313961
• 负责人: April Lukowski
• 金额: $ 6.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313961
• 关键词: Air; Algae; Anabolism; Animals; Bacteria; Bacterial Genes; Biochemical; Bivalvia; Bromine; Caribbean region; Catalysis; Chemicals; Collaborations; Consumption; Coupling; Cyanobacterium; Cytochrome P450; Data; Diet; Dolphins; Ecosystem; Electronics; Endocrine disruption; Environment; Environmental Health; Enzymatic Biochemistry; Enzymes; Fishes; Flame Retardants; Flavins; Food Chain; Food Webs; Furniture; Gammaproteobacteria; Generations; Genes; Genomics; Goals; Government; Health; Health Hazards; Homologous Gene; Hormone imbalance; Human; Infant Care; Institution; Kinetics; Letters; Life; Logic; Mammals; Metabolic Biotransformation; Metabolism; Metagenomics; Microbe; Molecular; Natural Products; Oceanography; Oceans; Organism; Oxidation-Reduction; Pathway interactions; Poison; Porifera; Production; Pseudoalteromonas; Red Algae; Research; Risk; Salmon; Sampling; Scombridae; Seafood; Seawater; Site-Directed Mutagenesis; Soil; Source; System; Thyroid Hormones; Time; Toxic effect; Tuna; Water; Whales; anthropogenesis; bioaccumulation; developmental disease; dietary; differential expression; environmental chemistry; enzyme biosynthesis; feeding; functional group; halogenation; insight; interest; man; metabolomics; metatranscriptomics; microbial community; microbiota; neurotoxicity; novel; ocean ecosystems; persistent organic pollutants; polybrominated diphenyl ether; seal; symbiont; transcriptomics

Project Summary/Abstract The presence of polybrominated diphenyl ethers (PBDEs) in the ocean has been a human health hazard since their implementation as flame retardants in the 1970s, causing a myriad of toxic effects including thyroid hormone imbalances, neurotoxicity, and developmental disorders. Since 2004, the entrance of anthropogenic PBDEs into the environment has been limited by government restrictions on their production. However, this environmental health crisis remains as PBDEs continue to be detected around the globe, impacting commonly consumed seafood, marine mammals, and humans. In 2005, it was discovered that not all PBDEs are of anthropogenic origin; commonly detected hydroxylated and methoxylated PBDEs (OH-BDEs and MeO-BDEs, respectively) were found to be natural products. Furthermore, the toxicity of OH-BDEs and MeO-BDEs were found to surpass that of anthropogenic PBDEs. Studies have demonstrated the persistence of PBDEs and their hydroxylated and methoxylated congeners in the environment and their ability to be passed through the food web; however, the handful of known OH/MeO-BDE bacterial and algal producers do not account for the global representation of the molecules in the oceans. Here, I propose to explore the possibility of novel OH/MeO-BDE producers by examining probable common dietary sources by searching for clues in sea water, ocean sediments, and marine animal-associated microbiota. This proposal aims to mine metagenomic and metatranscriptomic data from environmental samples to assess the distribution of OH/MeO-BDE producers in the environment and the chemistry employed in the biosynthetic machinery. The sequences of known OH/MeO-BDE biosynthesis enzymes from marine bacteria will be used initially as probes, followed by the use of biosynthetic logic to identify new enzymes of interest. In Aim 1, I will use this approach toward OH/MeO-BDE-producing red algae to establish, for the first time, the molecular basis for PBDE biosynthesis in an eukaryotic system. Differential expression analysis under low and high producing conditions will be employed to facilitate the identification of putative biosynthetic genes. In Aim 2, known bacterial genes and newly identified eukaryotic genes will be used as probes to assess metagenomic data from sea water, sediment, and marine animal associated microbes for the presence of PBDE biosynthesis genes. Finally, the enzymology of PBDE biosynthetic enzymes will be explored in Aim 3 to provide a detailed understanding of the underlying mechanisms of PBDE biosynthesis, specifically in the unique flavin dependent halogenases responsible for aromatic decarboxylative bromination. I anticipate that this research will provide an invaluable understanding of PBDE biosynthesis and its global distribution. Furthermore, this research will likely facilitate studies to manage PBDE production in the environment and provide new insights into understudied classes of enzymes.

项目总结/摘要 海洋中多溴联苯醚（PBDEs）的存在已对人类健康造成危害 自20世纪70年代作为阻燃剂使用以来，它们造成了无数的毒性影响，包括甲状腺 激素失衡、神经毒性和发育障碍。自2004年以来， 由于政府限制其生产，多溴联苯醚进入环境受到限制。但这 环境健康危机仍然存在，因为地球仪继续检测到多溴二苯醚， 食用海鲜海洋哺乳动物和人类2005年，人们发现并非所有的多溴二苯醚都是 人为来源;通常检测到的羟基化和甲氧基化多溴二苯醚（羟基溴二苯醚和甲氧基溴二苯醚， 它们都是天然产物。此外，羟基溴化二苯醚和甲氧基溴化二苯醚的毒性是 发现超过了人为的多溴二苯醚。研究表明，多溴二苯醚的持久性及其 环境中的羟基化和甲氧基化同系物及其通过食物的能力 然而，为数不多的已知OH/MeO-BDE细菌和藻类生产者并不占全球 海洋中分子的代表性。在这里，我建议探索新的OH/MeO-BDE的可能性 通过在海水、海洋沉积物中寻找线索， 和海洋动物相关的微生物群。 该提案旨在从环境样本中挖掘宏基因组和元转录组数据， 评估OH/MeO-BDE生产者在环境中的分布情况， 生物合成机器海洋细菌中已知的OH/MeO-BDE生物合成酶的序列将 最初用作探针，然后使用生物合成逻辑来鉴定感兴趣的新酶。在Aim中 1，我将使用这种方法对OH/MeO-BDE-生产红藻建立，第一次， 真核生物系统中多溴二苯醚生物合成的基础。低和高浓度下的差异表达分析 生产条件将被用于促进推定的生物合成基因的鉴定。在目标2中， 已知的细菌基因和新鉴定的真核基因将被用作探针来评估宏基因组 海水、沉积物和海洋动物相关微生物中存在多溴二苯醚生物合成的数据 基因.最后，目标3将探讨多溴二苯醚生物合成酶的酶学， 了解多溴二苯醚生物合成的基本机制，特别是在独特的黄素依赖性 负责芳香族脱羧溴化作用的卤化酶。我预计这项研究将提供一个 对多溴二苯醚生物合成及其全球分布的宝贵了解。此外，这项研究可能会 促进研究，以管理环境中的多溴二苯醚生产，并提供新的见解， 酶的种类