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.
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
Russell G
RG
Kerr
Amber C
AC
Kohl
Tyrone A
TA
Ferns
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