Studies of the cryptic allylic pyrophosphate isomerase activity of trichodiene synthase using the anomalous substrate 6,7-dihydrofarnesyl pyrophosphate.

  title={Studies of the cryptic allylic pyrophosphate isomerase activity of trichodiene synthase using the anomalous substrate 6,7-dihydrofarnesyl pyrophosphate.},
  author={David E Cane and John Lawrence Pawlak and R. Martinus Horak},
  volume={29 23},
Two enantiomeric analogues of farnesyl pyrophosphate (1) were tested as inhibitors and anomalous substrates of trichodiene synthase, which catalyzes the cyclization of trans,trans-farnesyl pyrophosphate (1) to the sesquiterpene hydrocarbon trichodiene (2). The reaction has been shown to involve preliminary isomerization of 1 to the tertiary allylic isomer nerolidyl pyrophosphate (3) which is cyclized without detectable release of the intermediate from the active site of the cyclase. Both (7S… 

The T296V Mutant of Amorpha-4,11-diene Synthase Is Defective in Allylic Diphosphate Isomerization but Retains the Ability To Cyclize the Intermediate (3R)-Nerolidyl Diphosphate to Amorpha-4,11-diene.

Analysis of additional mutants of amino acid residue 296 and in vitro assays demonstrated that the T296V mutant can no longer catalyze the allylic rearrangement of farnesyl diphosphate to the normal intermediate (3R,6E)-nerolidyl dphosphate, while retaining the ability to cyclization to amorphadiene.

A 1,6-ring closure mechanism for (+)-δ-cadinene synthase?

The results reported here do not unambiguously rule in favor of 1,6- or 1,10-cyclization, but demonstrate the mechanistic versatility inherent to DCS and highlight the possible existence of multiple mechanistic pathways.

Sesquiterpene Synthases Cop4 and Cop6 from Coprinus cinereus: Catalytic Promiscuity and Cyclization of Farnesyl Pyrophosphate Geometric Isomers

Investigation of the reaction mechanism and catalytic fidelity of two sesquiterpene synthases suggests that differences in the active site and the loop that covers theactive site of the two enzymes might explain their different catalytic fidelities.

Terpenoid cyclases: design and function of electrophilic catalysts.

  • D. Cane
  • Chemistry
    Ciba Foundation symposium
  • 1992
Insight into the architecture and function of the cyclase active site has come from the study of substrate and intermediate analogues designed to act as potential inhibitors or anomalous substrates of the normal cyclization reaction.

Multiproduct terpene synthases: catalytic promiscuity and cyclization of substrate geometric isomers

Terpenes constitute the largest and the most diverse class of natural products. The wealth of terpenes can be attributed to highly promiscuous enzymes called terpene synthases. Apart from single

Biosynthesis of (+)-cubenene and (+)-epicubenol by cell-free extracts of cultured cells of Heteroscyphus planus and cyclization of [^2H]farnesyl diphosphates

The absolute stereochemistry of cubenene and epicubenol from cultured cells of Heteroscyphus planus was determined as both (+)-isomers by 1H and 13C NMR spectroscopy, GLC using a chiral capillary

Trichodiene synthase: mechanism-based inhibition of a sesquiterpene cyclase.

  • D. CaneT. Bowser
  • Chemistry, Biology
    Bioorganic & medicinal chemistry letters
  • 1999



Synthesis of (E,Z)-α-,(Z,Z)-α-, and (Z)-β-farnesene

The three farnesenes (E,Z)-or-, (Z,Z)-or-, and (2)-P- were synthesized from (cis) (2)-nerolidol by dehydration with phosphoryl chloride in pyridine. The i.r., u.v., N.M.R., and mass spectra of the