Isoprenoids

Hotrienol (3, 7-dimethyl-1, 5, 7-octatrien-3-ol, II) is the principal aroma component detected by headspace analysis in leatherwood (Eucryphia lucida) honey. It arises from the dehydration of 2, 6-dimethyl-3, 7-octadiene-2, 6-diol (I), the principal terpene in methylated and unmethylated ether extracts of leatherwood honey. The diol I was detected in leatherwood plant extracts. Methylated ether extracts of the honey also contained methyl 2-hydroxy-2-(4-methoxyphenyl) acetate (III), which has not been previously reported in honey, in addition to many other aromatic substances. Compound III was a major component of the acidic fraction of the plant extract. A methylated extract of unripe leatherwood honey collected after 1 week in the hive was found to contain methyl 2-hydroxy-3-phenylpropionate (IV) and an unidentified compound [m/z 91 (100), 180] as the principal components. The unidentified compound found in immature honey was not detected in the plant extracts.

Azadirachta indica is a fast growing, evergreen tree
found commonly in India, Africa and America. Neem is one of
the most useful traditional medicinal plant in India. It is a highly
esteemed tree with several beneficial properties and applications,
especially known for its incredible therapeutic and
ethnomedicinal values for mankind. It has been used in different
medicinal systems: Ayurveda, unani, homeopathic medicine,
therefore considered as cynosure of modern medicine. Neem has
been used as the traditional medicine since a long time. The main
focus of research on Neem has been on the insecticidal properties
but in recent years investigations have expanded to the medicinal
utilizations as well. A large number of studies have been
published on the medicinal properties of Neem and Neem
extracts, covering a wide range of indications and ailments. The
present paper reviews the medicinal and therapeutical aspects of
Neem.

This work characterises volatile floral source descriptors for a variety of Australian unifloral honeys. The chemical analysis of naturally occurring honey volatiles is useful for authenticating the floral source of Australian honeys for domestic and overseas markets. Further, the floral and geographic origin of honey will need to be supplied by Australian honey exporters competing in the lucrative European market. With the European market, honey labelling now has to include information that shows the floral and geographical origin of the product, particularly if it is labelled as floral. Chemical fingerprinting of these volatiles has potential application to the authentication of the botanical source, which is of increasing commercial importance to the Australian honey industry in quality assurance programs.

This methodology was successfully applied to both Eucalyptus and non-Eucalyptus honey samples. Also, the components responsible for the strong, distinctive aroma and flavour of Australian honeys were identified. These, together with taste flavour compounds such as organic acids, make up the fiiU flavour of honey. In addition, high boiling semivolatiles are included in the flavour profile of honey. Floral source marker compounds for high quality unifloral (or 'straightline') samples of 11 floral types of Australian high quality species-specific or 'straightline' samples of floral honey have been identified using the volatile fraction. This flavour profile of volatile compounds represents a distinctive 'fingerprint' of the honey that can authenticate the floral source of the honey.

The three-step Floral Certification Test which has been developed involves firstly a solvent extraction of volatiles from honey, followed by their detection and quantification using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Finally, multivariate statistical analysis of the chemical data is performed. This methodology is applicable to any honey throughout the world once an initial survey is done on the composition of its volatile fraction. These procedures have permitted the identification of numerous compounds, including norisoprenoids, monoterpenes, benzene derivatives, aliphatic compounds, and Maillard reaction products. The characterisation of these volatiles is, therefore, of interest in the search for possible floral source descriptors for 11 floral types of Australian honey. The honeys studied were the eucalypt floral types, red gum, yapunyah, pilliga box, Caley's ironbark, spotted gum, and bloodwood; and the non-eucalypt floral types, crows ash, jelly bush, heath, tea tree and brush box.

The six eucalypt floral types of honey examined [red gum (E. camaldulensis), yapunyah (E. ochrophloia), pilliga box (E. pilligaenis), Caley's ironbark (E. caleyi), spotted gum (E. maculata) and bloodwood (E. intermedia)] were subjected to principal components analysis (PCA). A total of 21 variables (volatiles/groups of volatiles) were selected for these floral types of honey and analysed with corresponding published data on two eucalypt floral types of honey [yellow box (Eucalyptus melliodora) and blue gum (E. leucoxylon)]. These variables represent a diverse range of compound categories. In conclusion, it will be possible in the fiiture to authenticate these eight eucalypt floral types of honey using this methodology and the accimiulated chemical data summarised above, which will support quality assurance programs in the honey industry.

A total of five non-eucalypt floral types of honey were analysed. Each was considered separately with respect to the floral source descriptor volatiles and PCA of collected GC data. Crow ash (Guioa semiglauca) honey has some similarities to leatherwood honey, particularly related to monoterpene levels and variety.

Jelly bush (Leptospermum sp.) honey has some similarities to the New Zealand Leptospermum honeys, manuka and kanuka honeys. For jelly bush honey, GC analysis was able to distinguish between non-peroxide biologically active and inactive samples. The main distinguishing feature in the GC fingerprint of unmethylated extracts of active samples was a very large broad peak that elutes early and is absent in unmethylated extracts of inactive samples. When quantification of this compound(s) was combined with that for the other floral source descriptors, o-anisic acid (2-methoxybenzoic acid), dehydrovomifoliol, methyl syringate, and combined meso- and levo-butane-2,3-diols, and PCA of the data was undertaken, it is possible to authenticate non-peroxide active jelly bush honey samples from non-peroxide inactive ones.

For heath (Banksia ericifolia) honey and tea tee (Melaleuca quinguenervia) honey, there were similarities in the composition of volatiles. Floral source descriptors for these two floral types of honey were identified. Benzene derivatives were well represented amongst the volatiles floral source descriptors for these two honey types.

The final non-eucalypt honey studied in detail was brush box (Lophostemon conferta) honey. The composition of the volatile fraction of samples of this floral type was variable. Some unusual C9 and C10 norisoprenoids characterise this variety from other types.

In conclusion, this project has developed a rapid chemical procedure (Floral Certification Test based on 'chemical fingerprinting') for authenticating the floral origin of samples of species-specific floral types of Australian honey. The large amount of accumulated chemical data will support authenticity testing of floral Australian honeys in the future, as part of quality assurance programs of the Australian honey industry.

We evaluated the structure of planktonic communities and paleoenvironmental conditions throughout the Cenomanian–Turonian Oceanic Anoxic Event (OAE2) by studying bulk geochemical properties and the molecular isotopic composition of source-specific hydrocarbons from organic-rich sediments deposited in an intrashelf basin at the Levant Platform, central Jordan. High concentrations of desmethyl and 4-methylsteranes as well as dinosteranes indicate that marine algae including dinoflagellates were the main primary producing organisms. The presence of 2-methylhopanes and 13C-enriched hopanes, in addition to isotopically enriched aryl isoprenoids, evidenced the contribution of cyanobacteria and green sulfur bacteria, respectively. Additionally, variable but fairly low δ15N values during OAE2 suggest the occurrence of diazotrophy as a likely important process fueling primary production during OAE2 in this stratified/anoxic continental platform. Variations in the relative contribution of biomarkers revealed changes in planktonic communities associated with sea level change and water column stratification. OAE2 was characterized by strong stratification, anoxic bottom waters and a deep chemocline, as evidenced by high gammacerane and homohopane indices and the absence of photic zone euxinia (PZE) markers, respectively. However, the presence of isorenieratane and its derivatives in post-OAE black shales points to a shoaling of the chemocline and to PZE. This interval was also characterized by an exceptionally high abundance of chlorophyll-derived pristane and phytane (up to 2 mg g−1 TOC), likely as a result of highly enhanced primary production and organic matter preservation. Remarkably, this high productivity event co-occurs with an exceptionally high abundance of calcispheres reported elsewhere to be part of a global bio-event.

... Nicolas Chevalier a , Corresponding Author Contact Information , E-mail The Corresponding Author , Ioanna Bouloubassi a , Alina Stadnitskaia b , Marie-Hélène Taphanel a , Anne Lorre a , Jaap Sinninghe Damsté b and Catherine Pierre a. ...

The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures. Fosmidomycin is now-a-days prescribed clinically, however, less absorption, shorter half-life, and toxicity at higher doses, limits its use as an anti-malarial. The potential of other enzymes of the pathway as candidate drug targets has also been determined. This review details the various drug molecules tested against these targets with special emphasis to Plasmodium. We corroborate that MEP pathway functional within the apicoplast of Plasmodium is a major drug target, especially during erythrocytic stages. However, the major bottlenecks, bioavailability and toxicity of the new molecules needs to be addressed, before considering any new molecule as a potent antimalarial.

The most important Hungarian oil pools are located around the Mak6-H6dmez6v~is~irhely trench. Twenty-five oil samples have been studied from that area. The distributions and relative quantities of alkanes and isoprenoids (Cry-C20), steranes, triterpanes and aromatic steroid hydrocarbons were examined by gas chromatography and computerized gas chromatography-mass spectrometry. On the basis of biological marker compositions, the oils have been divided into three genetic groups and ranked in order of maturity. According to the investigations the major part of the oils is not derived from the above-mentioned trench as it was supposed before.

Staphylococcus species are a leading cause of skin and soft tissue infections in humans and animals, and the antibiotics used to treat these infections are often the same. Methicillin-and multidrug-resistant staphylococcal infections are becoming more common in human and veterinary medicine. From a " One Health " perspective, this overlap in antibiotic use and resistance raises concerns over the potential spread of antibiotic resistance genes. Whole-genome sequencing and comparative genomics analysis revealed that Staphylococcus species use divergent pathways to synthesize isoprenoids. Species frequently associated with skin and soft tissue infections in companion animals, including S. schleiferi and S. pseudinterme-dius, use the nonmevalonate pathway. In contrast, S. aureus, S. epidermidis, and S. lugdunensis use the mevalonate pathway. The antibiotic fosmidomycin, an inhibi-tor of the nonmevalonate pathway, was effective in killing canine clinical staphylo-coccal isolates but had no effect on the growth or survival of S. aureus and S. epider-midis. These data identify an essential metabolic pathway in Staphylococcus that differs among members of this genus and suggest that drugs such as fosmidomycin, which targets enzymes in the nonmevalonate pathway, may be an effective treatment for certain staphylococcal infections. IMPORTANCE Drug-resistant Staphylococcus species are a major concern in human and veterinary medicine. There is a need for new antibiotics that exhibit a selective effect in treating infections in companion and livestock animals and that would not be used to treat human bacterial infections. We have identified fosmidomycin as an antibiotic that selectively targets certain Staphylococcus species that are often encountered in skin infections in cats and dogs. These findings expand our understanding of Staphylococcus evolution and may have direct implications for treating staphylococcal infections in veterinary medicine.

Hotrienol (3,7-dimethyl-1,5,7-octatrien-3-01, 11) is the principal aroma component detected by headspace analysis in leatherwood (Eucryphia lucida) honey. It arises from the dehydration of 2,6-dimethyl-3,7-octadiene-2,6-diol (I), the principal terpene in methylated and unmethylated ether extracts of leatherwood honey. The diol I was detected in leatherwood plant extracts. Methylated ether extracts of the honey also contained methyl 2-hydroxy-2-(4-methoxyphenyl)acetate (1111, which has not been previously reported in honey, in addition to many other aromatic substances. Compound I11 was a major component of the acidic fraction of the plant extract. A methylated extract of unripe leatherwood honey collected after 1 week in the hive was found to contain methyl 2-hydroxy-3-phenylpropionate (N) and an unidentified compound [m /z 91 (loo), 1801 as the principal components. The unidentified compound found in immature honey was not detected in the plant extracts.

A study of the Liassic sequence in the Basque-Cantabrian Basin has shown the presence of organic-rich (TOC, HI and S 2 up to 8.7%, 760 and 56.5 mg/g, respectively) Pliensbachian-early Toarcian black shales that constitute the only feasible source rock for Ayoluengo oil. The ...

... Nicolas Chevalier a , Corresponding Author Contact Information , E-mail The Corresponding Author , Ioanna Bouloubassi a , Alina Stadnitskaia b , Marie-Hélène Taphanel a , Anne Lorre a , Jaap Sinninghe Damsté b and Catherine Pierre a. ...

The second enzyme in the methylerythritol phosphate pathway to isoprenoids, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR; EC 1.1.1.267) mediates the transformation of 1-deoxy-d-xylulose 5-phosphate (DXP) into 2-C-methyl-d-erythritol 4-phosphate. Several DXR mutants have been prepared to study amino acid residues important in binding or catalysis, but in-depth studies of many conserved residues in the flexible loop portion of the enzyme have not been conducted. In the course of our studies of this enzyme, an analog of DXP, 1,2-dideoxy-d-threo-3-hexulose 6-phosphate (1-methyl-DXP), was found to be a weak competitive inhibitor. Using the X-ray crystal structures of DXR as a guide, a highly conserved tryptophan residue in the flexible loop was identified that potentially blocks the use of this analog as a substrate. To test this hypothesis, four mutants of the Synechocystis sp. PCC6803 DXR were prepared and a W204F mutant was found to utilize the analog as a substrate.

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are analyzed in different lakes of the Mackenzie (Canadian Arctic) and Kolyma (Siberian Arctic) River basins to evaluate their sources and the implications for brGDGT-based paleothermometry in high latitude lakes. Comparison of brGDGT distributions and concentrations in the lakes with those in river suspended particulate matter (SPM), riverbank sediments, and permafrost material indicates that brGDGTs in Arctic lake sediments have mixed sources. In contrast to global observations, distributional offsets between brGDGTs in Arctic lakes and elsewhere in the catchment are minor, likely due to the extreme seasonality and short window of biological production at high latitudes. Consequently, both soil and lake calibrated brGDGT-based temperature proxies return sensible temperature estimates, even though the mean air temperature (MAT) in the Arctic is below the calibration range. The original soil-calibrated MBT-CBT (methylation of ...

Experimental and theoretical investigations concerning the second-to-last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants are reported. The proposed intrinsic or late intermediates 4-oxo-DMAPP (12) and 4-hydroxy-DMAPP (11) were synthesized in deuterium- or tritium-labeled form according to new protocols especially adapted to work without protection of the diphosphate moiety. When the labeled compounds MEcPP (7), 11, and 12 were applied to chromoplast cultures, aldehyde 12 was not incorporated. This finding is in agreement with a mechanistic and structural model of the responsible enzyme family: a three-dimensional model of the fragment L271–A375 of the enzyme GcpE of Streptomyces coelicolor including NADPH, the Fe4S4cluster, and MEcPP (7) as ligand has been developed based on homology modeling techniques. The model has been accepted by the Protein Data Bank (entry code 1OX2). Supported by this model, semiempirical PM3 calculations were performed to analyze the likely catalysis mechanism of the reductive ring opening of MEcPP (7), hydroxyl abstraction, and formation of HMBPP (8). The mechanism is characterized by a proton transfer (presumably from a conserved arginine 286) to the substrate, accompanied by a ring opening without high energy barriers, followed by the transfer of two electrons delivered from the Fe4S4cluster, and finally proton transfer from a carboxylic acid side chain to the hydroxyl group to be removed from the ligand as water. The proposed mechanism is in agreement with all known experimental findings and the arrangement of the ligand within the enzyme. Thus, a very likely mechanism for the second to last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants is presented. A principally similar mechanism is also expected for the reductive dehydroxylation of HMBPP (8) to IPP (9) and DMAPP (10) in the last step.