Biosynthesis and Genomics of Polybrominated Organic Compounds in the Marine Envi

卤代有机化合物在海洋食物网中的生物累积为人类接触若干类别的持久性有机污染物提供了直接途径。多溴联苯醚、多溴二苯并二恶英和多溴联吡咯等天然多溴有机化合物被认为是由蓝细菌和红藻等海洋生物合成的，涉及未知的代谢途径，其中含有尚未发现的卤化酶。该项目的目标是为海洋环境中HOCs的微生物生物合成提供遗传和生物化学基础。我们的研究 该战略包括对两个模式海洋细菌群体（假交替单胞菌和链霉菌）以及研究过程中发现的其他产生HOC的菌株中的多溴代代谢物生物合成进行全面的遗传、生物化学和酶结构分析。我们将提供一个直接的询问富含HOCs的天然maririe样品，以确定和表征这些生物合成途径在海洋环境中的流行程度。拟议的工作将由斯克里普斯的艾伦和摩尔实验室联合进行，他们在合作和联合学生指导方面有着良好的记录。该项目的成功是基于生物化学家，微生物学家，结构生物学家和基因组科学家的共同努力;因此，我们 已获得摩尔的长期合作伙伴约瑟夫诺埃尔教授（索尔克生物研究所，拉霍亚）的帮助，通过分包合同加入该项目，以协助溴化酶的蛋白质晶体学，从而详细了解酶溴化反应背后的结构基础。总的来说，这个项目将提供新的基于分子的有机卤素生物合成的见解，将与其他中心的调查，探索这些化合物的多样性和生态及其对海洋和人类健康的影响。 1

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