Tetrahymanol

Unusual fernane and gammacerane glycosides from the aerial parts of Spergula fallax.[Pubmed:24527835]

J Nat Prod. 2014 Mar 28;77(3):657-62.

The aerial parts of Spergula fallax afforded four glycosides (1-4) based on two new triterpene aglycones (1a and 2a), along with the known hopane glycoside succulentoside A. Compound 1 was identified as belonging to the fernane class, unusual migrated hopane triterpenoids, mainly isolated from ferns and only rarely from higher plants. Compounds 2-4 were assigned as gammacerane glycosides, having as aglycone a hydroxylated derivative of Tetrahymanol. The structures of the isolated compounds 1-4 and their aglycones 1a and 2a obtained by acid hydrolysis were elucidated by spectroscopic data interpretation. The growth inhibitory activity of the isolated compounds and their aglycones was evaluated against the HeLa and DLD-1 cancer cell lines.

Incomplete sterols and hopanoids pathways in ciliates: gene loss and acquisition during evolution as a source of biosynthetic genes.[Pubmed:24525200]

Mol Phylogenet Evol. 2014 May;74:122-34.

Polycyclic triterpenoids, such as sterols and hopanoids, are essential components of plasmatic membrane in eukaryotic organisms. Although it is generally assumed that ciliates do not synthesize sterols, and many of them are indeed auxotrophic, a large set of annotated genomic sequences and experimental data from recently studied organisms indicate that they can carry putative genes and respond to the presence/absence of precursors in various ways. The pre-squalene pathway, for instance, is largely present in all sequenced ciliates except in Ichthyophthirius multifiliis; although Paramecium tetraurelia lacks the squalene synthase and Oxytricha trifallax the squalene hopene synthase, in addition to the former. On the other hand, the post-squalene pathway, requiring oxygen in several steps, is mostly incomplete in all ciliates analyzed. Nevertheless, a number of predicted genes, with high sequence similarity to C-4 methyl oxidase/s, C-14 demethylase, C-5 and C-7 desaturases and C-24 reductase of sterols are found in Tetrahymena and Paramecium, and scattered in other Stichotrichia ciliates. Moreover, several of these sequences are present in multiples paralogs, like the C-7 desaturase in Paramecium, that carries six versions of the only one present in Tetrahymena. The phylogenetic analyses suggest a mixed origin for the genes involved in the biosynthesis of sterols and surrogates in this phylum; while the genes encoding enzymes of the pre-squalene pathway are most likely of bacterial origin, those involved in the post-squalene pathway, including the processing of sterols obtained from the environment, may have been partially retained or acquired indistinctly from lower eukaryotes or prokaryotes. This particular combination of diverse gene/s acquisition patterns allows for survival in conditions of poor oxygen availability, in which Tetrahymanol and other hopanoids may be advantageous, but also conditions of excess oxygen availability and abundant sterols, in which the latter are preferentially phagocyte, and/or transformed. Furthermore, the possibility that some of the genes involved in sterol metabolism may have another biological function in the most studied ciliate T. thermophila, was also explored.

Occurrence and sources of polar lipid tracers in sediments from the Shatt al-Arab River of Iraq and the northwestern Arabian Gulf.[Pubmed:24140688]

Sci Total Environ. 2014 Feb 1;470-471:180-92.

Shallow surface sediment samples from the southern part of the Shatt al-Arab River estuary of Iraq and the northwestern Arabian Gulf were analyzed for polar lipid compounds including n-alkanoic acids, n-alkanols, steroids and triterpenoids. The results showed that the n-alkanoic acids, methyl n-alkanoates and n-alkanols typically ranged from C12 to C32 with total concentrations of 3.2 to 108.2 mug g(-1)dwt sample, from C12 to C30 with totals of 1.1 to 18.9 mug g(-1)dwt sample, and from C14 to C32 at 1.8 to 112.6 mug g(-1)dwt sample, respectively. Steroids and triterpenoids were detected and included stenols, stanols, stenones, stanones, Tetrahymanol, tetrahymanone and extended betabeta-hopanes. The total steroid concentrations ranged from 2.8 to 78.4 mug g(-1)dwt sample, whereas the triterpenoids varied from 0.05 to 7.6 mug g(-1)dwt sample. The simple regression analysis of the results and the spatial distribution patterns of the identified organic tracers indicated that the inter-compound relationships were related mainly to their major sources. Cluster analysis and principal component analysis (PCA) of data set showed that the sampling sites are similar. These sources were allochthonous (terrestrial vegetation), autochthonous (plankton residues and bacteria in the sediments) and anthropogenic (sewage and petroleum).

Microbial Eukaryotes that Lack Sterols.[Pubmed:28509379]

J Eukaryot Microbiol. 2017 Nov;64(6):897-900.

It is widely held that sterols are key cyclic triterpenoid lipids in eukaryotic cell membranes and are synthesized through oxygen-dependent multienzyme pathways. However, there are known exceptions-ciliated protozoans, such as Tetrahymena, along with diverse low-oxygen-adapted eukaryotes produce, instead of sterols, the cyclic triterpenoid lipid Tetrahymanol that does not require molecular oxygen for its biosynthesis. Here, we report that a number of anaerobic microbial eukaryotes (protists) utilize neither sterols nor Tetrahymanol in their membranes. The lack of detectable sterol-like compounds in their membranes may provide an opportunity to reconsider the physiological function of sterols and sterol-like lipids in eukaryotes.

Hopanoid inventory of Rhodoplanes spp.[Pubmed:25935452]

Arch Microbiol. 2015 Aug;197(6):861-7.

Hopanoids are pentacyclic triterpenoid lipids and are important for bacterial membrane stability and functioning. These pentacyclic triterpenoids of hopane series are biomarkers for eubacteria and can be used as chemotaxonomic markers. Anoxygenic phototrophic bacteria are good producers of hopanoids, and their inventory to date is restricted to a few members. Rhodoplanes spp. are phototrophic prokaryotes which grow and thrive in subsurface and sediment environments. A study on the diversity of hopanoids of several species of Rhodoplanes revealed a rich diversity of hopanoids with carbon length of C30/C31 and C35. Hop-22(29)-ene (II), diplopterol (V), Tetrahymanol (VII), 2-methyldiplopterol (VI), 2-methylTetrahymanol (VIII), bacteriohopanetetrol (IX), bacteriohopaneaminotriol (X) and bacteriohopanepolyols [BHP-492 (XIII), BHP-550 (XIV), BHP-508 (XII)] are the major hopanoids of the genus Rhodoplanes. Tetrahymanol (VII) content is high (38-60 %) among all the members, except for Rhodoplanes elegans. Hopanoid fingerprints allowed differentiation of species of the genus Rhodoplanes. Statistical analyses also indicate hopanoids as good chemotaxonomic markers to distinguish species of the genus Rhodoplanes.

Oxidation of Fe(II) leads to increased C-2 methylation of pentacyclic triterpenoids in the anoxygenic phototrophic bacterium Rhodopseudomonas palustris strain TIE-1.[Pubmed:23480293]

Geobiology. 2013 May;11(3):268-78.

Hopanoids are among the most widespread biomarkers of bacteria that are used as indicators for past and present bacterial activity. Our understanding of the production, function, and distribution of hopanoids in bacteria has improved greatly, partly due to genetic, culture-independent studies. Culture-based studies are important to determine hopanoid function and the environmental conditions under which these compounds are produced. This study compares the lipid inventory of Rhodopseudomonas palustris strain TIE-1 under anoxic photoautotrophic conditions using either H2 or Fe(II) as electron donor. The high amount to which adenosylhopane is produced irrespective of the used electron donor suggests a specific function of this compound rather than its exclusive role as an intermediate in bacteriohopanepolyol biosynthesis. C-2 methylated hopanoids and Tetrahymanol account for as much as 59% of the respective C-2 methylated/non-methylated homologs during growth with Fe(II) as electron donor, as compared with 24% C-2 methylation for growth with H2 . This observation reveals that C-2 methylated hopanoids have a specific function and are preferentially synthesized in response to elevated Fe(II) concentrations. The presence of C-2 methylated pentacyclic triterpenoids has commonly been used as a biosignature for the interpretation of paleoenvironments. These new findings suggest that increased C-2 methylation may indicate anoxic ferrous conditions, in addition to other environmental stressors that have been previously reported.

A distinct pathway for tetrahymanol synthesis in bacteria.[Pubmed:26483502]

Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13478-83.

Tetrahymanol is a polycyclic triterpenoid lipid first discovered in the ciliate Tetrahymena pyriformis whose potential diagenetic product, gammacerane, is often used as a biomarker for water column stratification in ancient ecosystems. Bacteria are also a potential source of Tetrahymanol, but neither the distribution of this lipid in extant bacteria nor the significance of bacterial Tetrahymanol synthesis for interpreting gammacerane biosignatures is known. Here we couple comparative genomics with genetic and lipid analyses to link a protein of unknown function to Tetrahymanol synthesis in bacteria. This Tetrahymanol synthase (Ths) is found in a variety of bacterial genomes, including aerobic methanotrophs, nitrite-oxidizers, and sulfate-reducers, and in a subset of aquatic and terrestrial metagenomes. Thus, the potential to produce Tetrahymanol is more widespread in the bacterial domain than previously thought. However, Ths is not encoded in any eukaryotic genomes, nor is it homologous to eukaryotic squalene-Tetrahymanol cyclase, which catalyzes the cyclization of squalene directly to Tetrahymanol. Rather, heterologous expression studies suggest that bacteria couple the cyclization of squalene to a hopene molecule by squalene-hopene cyclase with a subsequent Ths-dependent ring expansion to form Tetrahymanol. Thus, bacteria and eukaryotes have evolved distinct biochemical mechanisms for producing Tetrahymanol.