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 by employing an unbiased metagenome mining approach. By 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.

Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca2+ Dynamics

“…For example, marine bacteria express enzymes that synthesize OH-PBDEs and their derivatives. 1,19–22 Like their anthropogenic counterparts, marine HOCs accumulate in marine mammals, Antarctic air, seabird eggs, and human breast milk, possibly adding to adverse health risks. 23–27 Recently, the biosynthetic pathways for a number of brominated pyrroles, bipyrroles and phenols have been also elucidated.…”

“…23–27 Recently, the biosynthetic pathways for a number of brominated pyrroles, bipyrroles and phenols have been also elucidated. 1,19,21,28 Tetrabromopyrrole ( 31 ) isolated from Pseudoalteromonas bacteria has been shown to elicit specific development cues to coral larvae necessary for metamorphosis and benthic attachment of Orbicella franksi and Acropora palmata onto crustose coralline algae. 29,30 Remarkably, high levels of several halopyrroles, including tetrabromopyrrole ( 31 ), are produced as disinfection byproducts (DBPs) during treatment of drinking water, agricultural irrigation water and saline wastewater, and are considered as emerging pollutants because of their cytotoxicity, genotoxicity, carcinogenicity and developmental toxicity.…”

Brominated Diphenyl Ethers Including a New Tribromoiododiphenyl Ether from the Vietnamese Marine Sponge Arenosclera sp. and Their Antibacterial Activities

“…Interestingly, one current report revealed that the cyanobacterium, Hormoscilla spongeliae (formerly Oscillatoria spongeliae), is the real producer of the polybrominated diphenyl ethers in Dysideidae sponges through the metagenome mining approach of the sponge-microbiome. [16] It is also proposed that cyanobacteria, Moorea producens, Pleurocapsa sp., and Rivularia sp. may produce these secondary metabolites.…”

An Overview on Marine Sponge-Symbiotic Bacteria as Unexhausted Sources for Natural Product Discovery

“…However, the production source of these PDBEs within these sponges was previously unknown. A study carried out by Agarwal et al [156] has now reported the discovery of biosynthetic gene clusters through the metagenome mining approach of the sponge-microbiome and identified association of these biosynthetic gene clusters within a sponge-associated cyanobacterial endosymbiont. Thus, investigating bioactive marine sponges through metagenomics may reveal the biosynthetic gene clusters which can then be incorporated into microorganisms that may be easily be grown within the laboratory [156].…”

“…'OSMAC' is the term for 'one strain many compounds', which is the ability of a single strain to produce different compounds when grown under differing conditions [156]. The culturing of a marine fungus, Spicaria elegans, which was grown under 10 different culture conditions was shown to produce a range of new compounds including the novel spicochalasin A, five new aspochalasins M-Q, and two known aspochalasins [234].…”