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The Role of Vanadium Bromoperoxidase in the Biosynthesis of Halogenated Marine Natural Products

  • Author(s): Franklin, Jayme N.
  • et al.
Abstract

The widespread occurrence of bromine- and chlorine-containing marine natural products has prompted investigations into the biosynthesis of halogenated marine metabolites. Halogenating enzymes, such as haloperoxidases, have long been thought to be involved in the biogenesis of halogenated marine natural products. Vanadium bromoperoxidases (V-BrPO) have been identified and isolated from all major classes of marine algae, and catalyze the two-electron oxidation of bromide by hydrogen peroxide.

To investigate V-BrPO in marine algae that produce halogenated natural products of interest, V-BrPO was cloned from four different red algae (Corallina officinalis, Plocamium cartilagineum, Delisea pulchra and Laurencia pacifica) using nucleotide probes based on a highly conserved sequence motif, P[S/A]YPSGHAT, for the class of vanadium haloperoxidases. Design of a bacterial expression system and subsequent kinetic characterization of recombinant and mutant forms of V-BrPO from C. officinalis were performed. In addition, steady state kinetics analysis of azide inhibition of V-BrPO from C. officinalis was completed.

V-BrPO was subsequently used to explore the biosynthesis ofbrominated terpene marine natural products. V-BrPO directed the bromination and cyclization of monoterpenes, including derivatives of geraniol to 5-, 6-, and 8-membered bromoether structures and brominated cyclized polyenes. In addition, V-BrPOre ctions with the sesquiterpene (+)-nerolidol resulted in the production of previously reported marine natural products a-and -snyderol, y-snyderol, and (+)- 3 -bromo-8-epicaparrapi oxide. V-BrPO catalyzed the asymmetric bromination of (+)-nerolidol to produce single diastereomers of brominated marine natural products.

V-BrPO identified at the surface of the marine red alga Delisea pulchra was shown to brominate 3-oxo-acyl homoserine lactones, thereby interrupting quorum sensing in Agrobacterium tumefaciens bioassays. V-BrPO isolated from D. pulchra was also shown to mediate the bromolactonization of 4-pentynoic acid in the biosynthesis of synthetic halogenated furanones.

The structures of siderophores, produced by the coastal marine bacterial isolate Vibrio sp. Roatan-10, were completed and membrane partitioning into large unilamellar phosphatidylcholine vesicles evaluated. Membrane partitioning coefficients for the physiological mixture of amphibactins was compared to previously reported data for marinobactin siderophores.

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