Enzymatic cyclization of all‐trans pentaprenyl and hexaprenyl methyl ethers by a cell‐free system from the protozoon Tetrahymena pyriformis

Abstract

A cell-free system from the protozoon Tetrahymenapyriforrnis capable of cyclizing squalene into tetrahymanol cyclizes all-trans pentaprenyl methyl ether to a scalarane-type sesterterpene and all-trans hexaprenyl methyl ether to bicyclo-, tricyclo-, tetracyclo-and pentacyclohexaprenyl methyl ethers, each corresponding to a possible cationic intermediate. The structures of the cyclization products have been determined by spectroscopic methods and are compatible with a biogenetic scheme involving polyprenyl ether cyclization. This is the first direct proof of an enzymatic cyclization of higher isoprenic alcohol derivatives, and we assume it was performed by the squalene-to-hopane cyclase of the protozoon. The formation of a scalarane-type sesterterpene from CZ5 polyprenyl methyl ether suggests that these terpenoids, whose presence is restricted to a few sponges, might be in fact microbial metabolites. Tricyclopolyprenyl derivatives have been identified in the organic matter from numerous sediments and they were interpreted as being chemical fossils of still unidentified microorganisms. The cyclization of hexaprenyl methyl ether is the first attempt of identification of these tricyclopolyprenol derivatives in living organisms.Some of the numerous microbial lipids have been discovered after the identification of their chemical fossils dispersed in the organic matter of sediments [l]. The ubiquitous geohopanoids are the most striking example: they have been found to be present, varied and abundant, in all sediments analyzed up to now, and they were found to be the molecular fossils of a new class of widespread and varied prokaryotic lipids, the microbial hopanoids [2, 31. The existence of other new classes of microbial lipids has been postulated by us from the wide distribution of still 'orphan' chemical fossils, plausible precursors of which were unknown in extant microorganisms [l]. These included, for instance, aliphathic glycerol ethers similar to the archaebacterial lipid ethers, the pentacyclic triterpene isoarborinol and the tricyclopolyprenols. The existence of the latter compounds in microorganisms was suggested by the identification of tricyclic sedimentary hydrocarbons in the CI9 to C45 range' [4-71. Biogenetically, these isoprenoids can be deduced from a proton-catalyzed cyclization of suitable regular polyprenol derivatives giving tricyclic compounds, the structures of which resemble those of some natural sesterterpenes isolated from a fern or a nudibranch [8,9]. Such cyclizations have already been studied in the biosynthesis of lower homologues from the mono-, sesqui-and diterpene series.Correspondence to M. Rohmer, Ecole Nationale Superieure de Chimie de Mulhouse, 3 rue Alfred Werner, F-68093 Mulhouse Cedex, France A bbreviutions. TLC, thin-layer chromatography; GLC, gas-liquid chromatography; MS, mass spectrometry; NMR, nuclear magnetic resonance.In an attempt to detect these isoprenoids in living organisms, we tried to cyclize tritium-labelled all-trans pentaprenol and hexaprenol derivatives with cell...

Sporulenes, Heptaprenyl Metabolites from Bacillus subtilis Spores

“…MS fragmentation patterns show features characteristic of the tetracyclic scalarane system ( 4 ), a sesterpene skeleton previously observed in metabolites isolated from marine sponges. (4) Additional fragments with m / z 119, 132, and 145 in all compounds are consistent with the presence of ethylene- (C 9 H 11 + ), propylene- (C 10 H 12 + ), and butylene-methylphenyl (C 11 H 13 + ) fragments, respectively, and indicate an aromatic side-chain moiety (Figure 1a).…”

A polycyclic terpenoid that alleviates oxidative stress

“…Our results show that regular polyprenes are natural substrates for the B. subtilis SqhC, and that this enzyme does not appear to be able to cyclize squalene in vitro (see SI Text). In contrast, studies of the squalene-hopene cyclase of Alicyclobacillus acidocaldarius and the tetrahymanol synthase of Tetrahymena pyriformis show that these enzymes are able to cyclize both squalene and regular polyprenes in vitro (12,13).…”

Superacid‐Catalyzed Cyclization of Methyl (6Z)‐Geranylfarnesoates

“…Biomimetic cyclization of long-chain polyprenols has also been investigated, and successful attempts of both enzymatic [3] and superacidic [4] cyclization have been reported; but only prenols with (all-E)-configuration have been used as substrates. On the other hand, it is known that most of the natural long-chain polyprenols possess the so-called di-trans-poly-cis or tri-trans-poly-cis configuration 1 ).…”