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Biosynthesis of polybrominated aromatic organic compounds by marine bacteria

Nature Chemical Biology volume 10, pages 640–647 (2014)Cite this article

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Abstract

Polybrominated diphenyl ethers (PBDEs) and polybrominated bipyrroles are natural products that bioaccumulate in the marine food chain. PBDEs have attracted widespread attention because of their persistence in the environment and potential toxicity to humans. However, the natural origins of PBDE biosynthesis are not known. Here we report marine bacteria as producers of PBDEs and establish a genetic and molecular foundation for their production that unifies paradigms for the elaboration of bromophenols and bromopyrroles abundant in marine biota. We provide biochemical evidence of marine brominases revealing decarboxylative-halogenation enzymology previously unknown among halogenating enzymes. Biosynthetic motifs discovered in our study were used to mine sequence databases to discover unrealized marine bacterial producers of organobromine compounds.

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Figure 1: Structures and sources of marine polybrominated natural products.
Figure 2: Genetic basis of the Bmp pathway.
Figure 3: In vitro reconstitution of activity for brominase Bmp2.
Figure 4: Biosynthesis of bromophenols by flavin-dependent decarboxylase-brominase Bmp5.
Figure 5: Enzymatic synthesis of polybrominated biphenyls and OH-BDEs.
Figure 6: Bi-modular scheme for the biosynthesis of polybrominated marine natural products by the bmp pathway.

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Acknowledgements

We thank our colleagues E. Frick for preliminary in vitro studies with Bmp6, B.M. Duggan for assistance in NMR data collection, P.A. Jordan for NMR data analysis, Y. Su for MS data collection and L.I. Aluwihare for useful discussions. This work was jointly supported by the US National Science Foundation (OCE-1313747) and the US National Institute of Environmental Health Sciences (P01-ES021921) through the Oceans and Human Health program, the Gordon and Betty Moore Foundation Marine Microbial Sequencing Project, the Helen Hay Whitney Foundation postdoctoral fellowship to V.A., the US National Institutes of Health (NIH) Marine Biotechnology Training Grant predoctoral fellowship to A.A.E. (T32-GM067550) and an NIH instrument grant (S10-RR031562).

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Author notes

  1. Kazuya Yamanaka & Roland D Kersten

    Present address: Present address: JNC Corporation, Yokohama Research Center, Yokohama, Japan (K.Y.); Salk Institute for Biological Studies, San Diego, California, USA (R.D.K.).,

  2. Vinayak Agarwal and Abrahim A El Gamal: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Oceans and Human Health, Scripps Institution of Oceanography, University of California–San Diego, La Jolla, California, USA

    Vinayak Agarwal, Abrahim A El Gamal, Eric E Allen & Bradley S Moore

  2. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California–San Diego, La Jolla, California, USA

    Kazuya Yamanaka, Dennis Poth, Roland D Kersten, Michelle Schorn, Eric E Allen & Bradley S Moore

  3. Division of Biological Sciences, University of California–San Diego, La Jolla, California, USA

    Eric E Allen

  4. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego, La Jolla, California, USA

    Bradley S Moore

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  1. Vinayak Agarwal
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Contributions

V.A., A.A.E., E.E.A. and B.S.M. designed research; V.A., A.A.E. and K.Y. performed genetic experiments; V.A., A.A.E. and R.D.K. performed in vitro experiments; M.S. and E.E.A. generated sequencing data; D.P. contributed new analytical reagents; and V.A., A.A.E., E.E.A. and B.S.M. analyzed data and wrote the manuscript.

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Correspondence to Bradley S Moore.

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Agarwal, V., El Gamal, A., Yamanaka, K. et al. Biosynthesis of polybrominated aromatic organic compounds by marine bacteria. Nat Chem Biol 10, 640–647 (2014). https://doi.org/10.1038/nchembio.1564

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