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: 10471212
• 负责人: April Lukowski
• 金额: $ 6.76万
• 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/10471212
• 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; 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.

项目摘要/摘要 海洋中多溴二苯基醚（PBDE）的存在一直是人类健康危害 由于它们在1970年代将其作为阻燃剂的实施，因此导致无数的有毒作用包括甲状腺 激素失衡，神经毒性和发育障碍。自2004年以来，人为 PBDE进入环境受到政府对其生产的限制的限制。但是，这个 由于PBDE在全球范围内继续发现，环境健康危机仍然存在，通常会影响 消耗海鲜，海洋哺乳动物和人类。在2005年，发现并非所有PBDE都是 人为来源；通常检测到的羟基化和甲氧基化的PBDE（OH-BDES和MEO-BDES， 发现分别是天然产物。此外，OH-BDE和MEO-BDE的毒性是 发现超过了人为PBDE的。研究表明，PBDE及其持久性 环境中的羟基化和甲氧基化同类物及其通过食物的能力 网络；但是，少数已知的OH/MEO-BDE细菌和藻类生产商不考虑全球 海洋分子的表示。在这里，我建议探索小说的可能性哦/Meo-bde 通过在海水，海洋沉积物中寻找可能的线索来检查可能的常见饮食来源， 和海洋动物相关的微生物群。 该建议旨在挖掘从环境样本到 评估OH/MEO-BDE生产商在环境中的分布以及在 生物合成机械。来自海洋细菌的已知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识别感兴趣的新酶。目标 1，我将使用这种方法来实现OH/MEO-BDE产生的红色藻类，以首次建立分子 真核系统中PBDE生物合成的基础。低和高的差异表达分析 生产条件将用于促进假定的生物合成基因的鉴定。在AIM 2中， 已知的细菌基因和新鉴定的真核基因将用作评估宏基因组学的探针 海水，沉积物和海洋动物相关的微生物的数据，用于存在PBDE生物合成 基因。最后，将在AIM 3中探索PBDE生物合成酶的酶学，以提供详细的 了解PBDE生物合成的潜在机制，特别是在独特的黄素依赖性中 负责芳二羧基溴化的卤代酶。我预计这项研究将提供 对PBDE生物合成及其全球分布的宝贵理解。此外，这项研究可能会 促进研究在环境中管理PBDE生产的研究，并提供新的见解 酶类。