Enzymatic Reductive Dehalogenation Controls the Biosynthesis of Marine Bacterial Pyrroles.
Enzymes capable of performing dehalogenating reactions have attracted tremendous contemporary attention due to their potential application in the bioremediation of anthropogenic polyhalogenated persistent organic pollutants. Nature, in particular the marine environment, is also a prolific source of polyhalogenated organic natural products. The study of the biosynthesis of these natural products has furnished a diverse array of halogenation biocatalysts, but thus far no examples of dehalogenating enzymes have been reported from a secondary metabolic pathway. Here we show that the penultimate step in the biosynthesis of the highly brominated marine bacterial product pentabromopseudilin is catalyzed by an unusual debrominase Bmp8 that utilizes a redox thiol mechanism to remove the C-2 bromine atom of 2,3,4,5-tetrabromopyrrole to facilitate oxidative coupling to 2,4-dibromophenol. To the best of our knowledge, Bmp8 is first example of a dehalogenating enzyme from the established genetic and biochemical context of a natural product biosynthetic pathway.
Center for Oceans and Human Health, Scripps Institution of Oceanography, Scripps Institution of Oceanography, University of California, San Diego , San Diego, California 92093, United States.
Abrahim
A
El Gamal
Center for Oceans and Human Health, Scripps Institution of Oceanography, Scripps Institution of Oceanography, University of California, San Diego , San Diego, California 92093, United States.
Vinayak
V
Agarwal
Center for Oceans and Human Health, Scripps Institution of Oceanography, Scripps Institution of Oceanography, University of California, San Diego , San Diego, California 92093, United States.
Imran
I
Rahman
Center for Oceans and Human Health, Scripps Institution of Oceanography, Scripps Institution of Oceanography, University of California, San Diego , San Diego, California 92093, United States.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , San Diego, California 92093, United States.
Bradley S
BS
Moore
D059001:Aquatic Organisms / Q000201:enzymology / Q000378:metabolism*; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D054879:Halogenation; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*
D011758:Pyrroles
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