Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges

Abstract

Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most prolific sources, marine sponges of the order Dysideidae, remains unidentified. Here, we report the discovery of PBDE biosynthetic gene clusters within sponge-microbiome-associated cyanobacterial endosymbionts through the use of an unbiased metagenome-mining approach. Using expression of PBDE biosynthetic genes in heterologous cyanobacterial hosts, we correlate the structural diversity of naturally produced PBDEs to modifications within PBDE biosynthetic gene clusters in multiple sponge holobionts. Our results establish the genetic and molecular foundation for the production of PBDEs in one of the most abundant natural sources of these molecules, further setting the stage for a metagenomic-based inventory of other PBDE sources in the marine environment.

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Figure 1: Synthetic and naturally occurring polyhalogenated molecules.
Figure 2: Host and symbiont phylogenies.
Figure 3: Representative 16S rRNA gene diversity profiles.
Figure 4: Discovery of hs_bmp gene clusters.
Figure 5: Functional characterization of Clade Ia hs_bmp genes.

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Acknowledgements

We thank our colleague B.M. Duggan at the University of California, San Diego for assistance in acquiring NMR data. This work was supported by the US National Science Foundation (DGE-1144086 Graduate Research Fellowship to J.M.B., OCE-1313747 to P.R.J., E.E.A., and B.S.M., IOS-1120113 to J.S.B., MCB-1149552 to E.E.A.); the US National Institutes of Health (K99ES026620 to V.A., R01-GM107557 to E.W.S., P01-ES021921 to P.R.J., E.E.A., and B.S.M., R01-CA172310 to V.J.P., instrument grant S10-OD010640); the US Department of Energy (DE-EE0003373 to J.W.G.); and the Helen Hay Whitney Foundation postdoctoral fellowship to V.A.

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V.A., S.P., A.T., E.W.S., V.J.P., E.E.A., and B.S.M. designed the study. V.A. performed chemical characterization; V.A., A.T., and J.W.G. performed cyanobacterial expression experiments; J.M.B., M.A.S., J.B., and P.R.J. performed phylogenetic analyses; S.P. performed metagenomic analyses; Z.L., V.J.P., and J.S.B. provided sponge samples, analytical tools and reagents; and V.A., J.M.B., S.P., E.E.A., and B.S.M. wrote the manuscript with input from all authors.

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Correspondence to Eric E Allen or Bradley S Moore.

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Supplementary Results, Supplementary Tables 1–9 and Supplementary Figures 1–10 (PDF 2151 kb)

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NMR Characterization Data (PDF 853 kb)

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Agarwal, V., Blanton, J., Podell, S. et al. Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges. Nat Chem Biol 13, 537–543 (2017). https://doi.org/10.1038/nchembio.2330

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