1.Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.
Harris GG1, Lombardi PM1, Pemberton TA1, Matsui T2, Weiss TM2, Cole KE1, Köksal M1, Murphy FV 4th3, Vedula LS1, Chou WK4, Cane DE4, Christianson DW1,5. Biochemistry. 2015 Dec 8;54(48):7142-55. doi: 10.1021/acs.biochem.5b01143. Epub 2015 Nov 24.
Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg(2+) for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with three Mg(2+) ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis.
2.Fractionation and identification of minor and aroma-active constituents in Kangra orthodox black tea.
Joshi R1, Gulati A2. Food Chem. 2015 Jan 15;167:290-8. doi: 10.1016/j.foodchem.2014.06.112. Epub 2014 Jul 5.
The aroma constituents of Kangra orthodox black tea were isolated by simultaneous distillation extraction (SDE), supercritical fluid extraction and beverage method. The aroma-active compounds were identified using gas chromatography-olfactometry-mass spectrometry. Geraniol, linalool, (Z/E)-linalool oxides, (E)-2-hexenal, phytol, β-ionone, hotrienol, methylpyrazine and methyl salicylate were major volatile constituents in all the extracts. Minor volatile compounds in all the extracts were 2-ethyl-5-methylpyrazine, ethylpyrazine, 2-6,10,14-trimethyl-2-pentadecanone, acetylfuran, hexanoic acid, dihydroactinidiolide and (E/Z)-2,6-nonadienal. The concentrated SDE extract was fractionated into acidic, basic, water-soluble and neutral fractions. The neutral fraction was further chromatographed on a packed silica gel column eluted with pentane and diethyl ether to separate minor compounds. The aroma-active compounds identified using gas chromatography-olfactometry-mass spectrometry were 2-amylfuran, (E/Z)-2,6-nonadienal, 1-pentanol, epoxylinalool, (Z)-jasmone, 2-acetylpyrrole, farnesyl acetone, geranyl acetone, cadinol, cubenol and dihydroactinidiolide.
3.Nucleolipids of the cancerostatic 5-fluorouridine: synthesis, adherence to oligonucleotides, and incorporation in artificial lipid bilayers.
Malecki E1, Ottenhaus V, Werz E, Knies C, Montilla Martinez M, Rosemeyer H. Chem Biodivers. 2014 Feb;11(2):217-32. doi: 10.1002/cbdv.201300127.
5-Fluorouridine (1a) was converted to its N(3)-farnesylated nucleoterpene derivative 8 by direct alkylation with farnesyl bromide (4). Reaction of the cancerostatic 1a with either acetone, heptan-4-one, nonadecan-10-one, or hentriacontan-16-one afforded the 2',3'-O-ketals 2a-2d. Compound 2b was then first farnesylated (→5) and subsequently phosphitylated to give the phosphoramidite 6. The ketal 2c was directly 5'-phosphitylated without farnesylation of the base to give the phosphoramidite 7. Moreover, the recently prepared cyclic 2',3'-O-ketal 11 was 5'-phosphitylated to yield the phosphoramidite 12. The 2',3'-O-isopropylidene derivative 2a proved to be too labile to be converted to a phosphoramidite. All novel derivatives of 1a were unequivocally characterized by NMR and UV spectroscopy and ESI mass spectrometry, as well as by elemental analyses. The lipophilicity of the phosphoramidite precursors were characterized by both their retention times in RP-18 HPLC and by calculated log P values.
4.Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity.
Bonikowski R1, Świtakowska P2, Sienkiewicz M3, Zakłos-Szyda M4. Molecules. 2015 Jun 18;20(6):11272-96. doi: 10.3390/molecules200611272.
By implementing a common and industrially used method, 30 compounds which are structurally related to geranyl acetone, nerolidol, farnesal, farnesol and farnesyl acetate were obtained. Their antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was investigated. Pharmacophore models were proposed based on the obtained results and 3D QSAR modelling. Cytotoxic effects against mainly human immortalised and normal cell lines of different origin (malignant melanoma MeWo, colorectal adenocarcinoma HT29, promyelocytic leukemia HL60, gingival fibroblasts HFIG, skin keratinocytes HaCaT and rat small intestine epithelium IEC6) were examined. The odour descriptions of newly synthesised compounds are given.