The bioaccumulation of halogenated organic compounds (HOCs) in the marine food web provides a direct route for human exposure to several classes of persistent organic pollutants. Natural polybrominated organic compounds such as polybrominated diphenyl ethers, polybrominated dibenzodioxins and polybrominated bipyrroles are collectively proposed to be synthesized by marine organisms such as cyanobacteria and red algae involving unknown metabolic pathways harboring yet to be discovered halogenating enzymes. The goals of this project are to provide a genetic and biochemical foundation for the microbial biosynthesis of HOCs in the marine environment. Our research strategy includes a comprehensive genetic, biochemical, and enzyme structure-based analysis of polybrominated metabolite biosynthesis in two model marine bacterial groups, Pseudoalteromonas and Streptomyces, as well as other HOC producing strains discovered in the course of the research. We will provide a direct interrogation of natural maririe samples enriched in HOCs to identify and characterize the prevalence of these biosynthetic pathways in the marine environment. The proposed work will be undertaken jointly by the laboratories of Allen and Moore at Scripps who have a proven track record of collaboration and joint student mentorship. The success of this Project is based on biochemists, microbiologists, structural biologists and genome scientists working together;thus we have enlisted the help of Moore's long-standing collaborator Prof. Joseph Noel (Salk Institute for Biological Studies, La Jolla) to join the Project through a sub-contract to assist in the protein crystallography of brominating enzymes in order to provide a detailed understanding of the structural basis behind enzymatic bromination. Collectively, this project will deliver new molecular-based insight into organohalogen biosynthesis that will be united with other Center investigations to explore the diversity and ecology of these compounds and their impacts on oceans and human health. 1

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES021921-02
Application #
8550046
Study Section
Special Emphasis Panel (ZES1-LKB-J)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$114,918
Indirect Cost
$35,793
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
El Gamal, Abrahim; Agarwal, Vinayak; Diethelm, Stefan et al. (2016) Biosynthesis of coral settlement cue tetrabromopyrrole in marine bacteria by a uniquely adapted brominase-thioesterase enzyme pair. Proc Natl Acad Sci U S A 113:3797-802
El Gamal, Abrahim; Agarwal, Vinayak; Rahman, Imran et al. (2016) Enzymatic Reductive Dehalogenation Controls the Biosynthesis of Marine Bacterial Pyrroles. J Am Chem Soc 138:13167-13170
Teufel, Robin; Agarwal, Vinayak; Moore, Bradley S (2016) Unusual flavoenzyme catalysis in marine bacteria. Curr Opin Chem Biol 31:31-9
Harvey, Elizabeth L; Deering, Robert W; Rowley, David C et al. (2016) A Bacterial Quorum-Sensing Precursor Induces Mortality in the Marine Coccolithophore, Emiliania huxleyi. Front Microbiol 7:59
Agarwal, Vinayak; Li, Jie; Rahman, Imran et al. (2015) Complexity of naturally produced polybrominated diphenyl ethers revealed via mass spectrometry. Environ Sci Technol 49:1339-46
Hong, Mee Young; Lumibao, Jan; Mistry, Prashila et al. (2015) Fish Oil Contaminated with Persistent Organic Pollutants Reduces Antioxidant Capacity and Induces Oxidative Stress without Affecting Its Capacity to Lower Lipid Concentrations and Systemic Inflammation in Rats. J Nutr 145:939-44
Agarwal, Vinayak; Diethelm, Stefan; Ray, Lauren et al. (2015) Chemoenzymatic Synthesis of Acyl Coenzyme A Substrates Enables in Situ Labeling of Small Molecules and Proteins. Org Lett 17:4452-5
Ross, Avena C; Gulland, Lauren E S; Dorrestein, Pieter C et al. (2015) Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. ACS Synth Biol 4:414-20
Millow, Christopher J; Mackintosh, Susan A; Lewison, Rebecca L et al. (2015) Identifying bioaccumulative halogenated organic compounds using a nontargeted analytical approach: seabirds as sentinels. PLoS One 10:e0127205
Shaul, Nellie J; Dodder, Nathan G; Aluwihare, Lihini I et al. (2015) Nontargeted biomonitoring of halogenated organic compounds in two ecotypes of bottlenose dolphins (Tursiops truncatus) from the Southern California Bight. Environ Sci Technol 49:1328-38

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