Elucidation of the biosynthetic origin of the anti-inflammatory pseudopterosins

J Ind Microbiol Biotechnol. 2006 Jul;33(7):532-8. doi: 10.1007/s10295-006-0106-3. Epub 2006 Mar 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Diterpenes* / analysis
  • Diterpenes* / chemistry
  • Glycosides / biosynthesis*
  • Glycosides / chemistry
  • Oxidation-Reduction
  • Pseudomonas / enzymology
  • Pseudomonas / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diterpenes
  • Glycosides
  • elisabethatriene
  • pseudopterosins