Elucidation of the biosynthetic origin of the anti-inflammatory pseudopterosins.
The pseudopterosins are a family of diterpene glycosides isolated from the gorgonian coral Pseudopterogorgia elisabethae. These metabolites exhibit potent anti-inflammatory activity, and this review describes our efforts to elucidate their biosynthetic origin. A radioactivity-guided isolation was used to identify the terpene cyclase product. In addition, a detailed NMR-guided search for potential biosynthetic intermediates identified metabolites which were tested by incubating 3H-labeled analogues with a cell-free extract of the coral. All labeled metabolites were generated biosynthetically, and radiochemical purity was established by a combination of HPLC purification and derivatization. In summary, pseudopterosins are produced by a cyclization of geranylgeranyl diphosphate to elisabethatriene, aromatization to erogorgiaene, two successive oxidations to 7,8-dihydroxyerogorgiaene and a glycosylation to afford a seco-pseudopterosin as a key intermediate. A dehydrogenation leads to amphilectosins which undergo ring closures to yield the pseudopterosins.
Kerr
Russell G
RG
Department of Chemistry and Biochemistry, and Center of Excellence in Biomedical and Marine Biotechnology, Florida Atlantic University, Boca Raton, FL 33431, USA. rkerr@fau.edu
Kohl
Amber C
AC
Ferns
Tyrone A
TA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D004224:Diterpenes / Q000032:analysis / Q000737:chemistry; D006027:Glycosides / Q000096:biosynthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D011549:Pseudomonas / Q000201:enzymology / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D006027:Glycosides; C516495:elisabethatriene; C049922:pseudopterosins