Vanadium bromoperoxidase-catalyzed biosynthesis of halogenated marine natural products.
Marine red algae (Rhodophyta) are a rich source of bioactive halogenated natural products. The biogenesis of the cyclic halogenated terpene marine natural products, in particular, has attracted sustained interest in part because terpenes are the biogenic precursors of many bioactive metabolites. The first enzymatic asymmetric bromination and cyclization of a terpene, producing marine natural products isolated from red algae, is reported. Vanadium bromoperoxidase (V-BrPO) isolated from marine red algae (species of Laurencia, Plocamium, Corallina) catalyzes the bromination of the sesquiterpene (E)-(+)-nerolidol producing alpha-, beta-, and gamma-snyderol and (+)-3beta-bromo-8-epicaparrapi oxide. alpha-Snyderol, beta-snyderol, and (+)-3beta-bromo-8-epicaparrapi oxide have been isolated from Laurencia obtusa, and each have also been isolated from other species of marine red algae. gamma-Snyderol is a proposed intermediate in other bicyclo natural products. Single diastereomers of beta-snyderol, gamma-snyderol, and mixed diastereomers of (+)-3beta-bromo-8-epicaparrapi oxide (de = 20-25%) are produced in the enzyme reaction, whereas two diastereomers of these compounds are formed in the synthesis with 2,4,4,6-tetrabromocyclohexa-2,5-dienone (TBCO). V-BrPO likely functions by catalyzing the two-electron oxidation of bromide ion by hydrogen peroxide producing a bromonium ion or equivalent in the active site that brominates one face of the terminal olefin of nerolidol. These results establish V-BrPO's role in the biosynthesis of brominated cyclic sesquiterpene structures from marine red algae for the first time.
Carter-Franklin
Jayme N
JN
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106-9510, USA.
Butler
Alison
A
D000818:Animals; D001966:Bromine / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006842:Hydrocarbons, Brominated / Q000378:metabolism*; D007700:Kinetics; D010544:Peroxidases / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000737:chemistry / Q000378:metabolism; D000461:Rhodophyta / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
D006842:Hydrocarbons, Brominated; D012717:Sesquiterpenes; D010544:Peroxidases; C026195:bromide peroxidase; D010637:Phenolsulfonphthalein; C037055:nerolidol; D001966:Bromine