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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

基本信息

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
项目类别：
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

项目摘要

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/文摘