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211.
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Timo Heinrich Hans-Peter Buchstaller Bertram Cezanne Felix Rohdich Jörg Bomke Manja Friese-Hamim Mireille Krier Thorsten Knöchel Djordje Musil Birgitta Leuthner Frank Zenke 《Bioorganic & medicinal chemistry letters》2017,27(3):551-556
The natural product fumagillin 1 and derivatives like TNP-470 2 or beloranib 3 bind to methionine aminopeptidase 2 (MetAP-2) irreversibly. This enzyme is critical for protein maturation and plays a key role in angiogenesis. In this paper we describe the synthesis, MetAP-2 binding affinity and structural analysis of reversible MetAP-2 inhibitors. Optimization of enzymatic activity of screening hit 10 (IC50: 1 μM) led to the most potent compound 27 (IC50: 0.038 μM), with a concomitant improvement in LLE from 2.1 to 4.2. Structural analysis of these MetAP-2 inhibitors revealed an unprecedented conformation of the His339 side-chain imidazole ring being co-planar sandwiched between the imidazole of His331 and the aryl-ether moiety, which is bound to the purine scaffold. Systematic alteration and reduction of H-bonding capability of this metal binding moiety induced an unexpected 180° flip for the triazolo[1,5-a]pyrimdine bicyclic template. 相似文献
213.
Karima Hezbri Imen Nouioui Manfred Rohde Peter Schumann Maher Gtari Hans-Peter Klenk Maria del Carmen Montero-Calasanz Faten Ghodhbane-Gtari 《Antonie van Leeuwenhoek》2017,110(3):339-346
The taxonomic position of an actinobacterial isolate, designated strain BMG 822T, isolated from limestone from the Amphitheater of El Jem (Coliseum Thysdrus), Tunisia, was established using a polyphasic approach. Strain BMG 822T was found to grow well at 30 °C and pH 6.5–8.0, and to be coral-coloured, Gram-positive, catalase and oxidase negative. Whole cell hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid, glucose, galactose and ribose. The phospholipids detected were diphosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, an unidentified glycophospholipid and six unidentified phospholipids. MK-9(H4) was found to be the predominant menaquinone, followed by MK-9(H2) and MK-9. The major cellular fatty acids were identified as iso-C16:0, C18:1 ω9c, C17:1 ω8c and iso-H-C16:1. The G+C content of the DNA (73.2%) is typical of the genus. High degrees of 16S rRNA gene sequence similarity were found with the type strains of the genus Blastococcus (97.1–98.3%) followed by the type strains of Modestobacter (96.8–97.8%). Based on the above data and the phenotypic differences from the type strains of Blastococcus species, it is proposed that the isolate BMG 822T (=DSM 46837T=CECT 8823T) should be classified as the type strain of a novel species, Blastococcus colisei sp. nov. 相似文献
214.
Khaoula Bouznada Noureddine Bouras Salim Mokrane Fawzia Chaabane Chaouch Abdelghani Zitouni Gabriele Pötter Cathrin Spröer Hans-Peter Klenk Nasserdine Sabaou 《Antonie van Leeuwenhoek》2017,110(3):399-405
The taxonomic position of a new Saccharothrix strain, designated MB46T, isolated from a Saharan soil sample collected in Mzab region (Ghardaïa province, South Algeria) was established following a polyphasic approach. The novel microorganism has morphological and chemical characteristics typical of the members of the genus Saccharothrix and formed a phyletic line at the periphery of the Saccharothrix espanaensis subcluster in the 16S rRNA gene dendrograms. Results of the 16S rRNA gene sequence comparisons revealed that strain MB46T shares high degrees of similarity with S. espanaensis DSM 44229T (99.2%), Saccharothrix variisporea DSM 43911T (98.7%) and Saccharothrix texasensis NRRL B-16134T (98.6%). However, the new strain exhibited only 12.5–17.5% DNA relatedness to the neighbouring Saccharothrix spp. On the basis of phenotypic characteristics, 16S rRNA gene sequence comparisons and DNA-DNA hybridizations, strain MB46T is concluded to represent a novel species of the genus Saccharothrix, for which the name Saccharothrix ghardaiensis sp. nov. (type strain MB46T = DSM 46886T = CECT 9046T) is proposed. 相似文献
215.
The self‐sufficient P450 RhF expressed in a whole cell system selectively catalyses the 5‐hydroxylation of diclofenac
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Jan M. Klenk Bernd A. Nebel Joanne L. Porter Justyna K. Kulig Shaneela A. Hussain Sven M. Richter Michele Tavanti Nicholas J. Turner Martin A. Hayes Bernhard Hauer Sabine L. Flitsch 《Biotechnology journal》2017,12(3)
P450 monooxygenases are able to catalyze the highly regio‐ and stereoselective oxidations of many organic molecules. However, the scale‐up of such bio‐oxidations remains challenging due to the often‐low activity, level of expression and stability of P450 biocatalysts. Despite these challenges they are increasingly desirable as recombinant biocatalysts, particularly for the production of drug metabolites. Diclofenac is a widely used anti‐inflammatory drug that is persistent in the environment along with the 4'‐ and 5‐hydroxy metabolites. Here we have used the self‐sufficient P450 RhF (CYP116B2) from Rhodococcus sp. in a whole cell system to reproducibly catalyze the highly regioselective oxidation of diclofenac to 5‐hydroxydiclofenac. The product is a human metabolite and as such is an important standard for environmental and toxicological analysis. Furthermore, access to significant quantities of 5‐hydroxydiclofenac has allowed us to demonstrate further oxidative degradation to the toxic quinoneimine product. Our studies demonstrate the potential for gram‐scale production of human drug metabolites through recombinant whole cell biocatalysis. 相似文献
216.
Hans-Peter Stika 《Vegetation History and Archaeobotany》2005,14(3):189-197
The early Neolithic sites of La Lámpara and La Revilla del Campo in the Meseta Norte (Northern Meseta) plateau in central Spain produced evidence for early agriculture from the last third of the 6th millennium B.C. The hulled wheats Triticum monococcum (einkorn) and T. dicoccum (emmer) were identified from carbonised plant remains as well as from imprints in pottery and daub. Single finds of charred remains of Hordeum vulgare (barley), Papaver somniferum/setigerum (poppy) and Linum usitatissimum (linseed) indicated other cultivated crops. The wild plants mainly indicated arable weeds, partly from less fertile soils, and garrigue vegetation from poor pastures. The spectrum of crops from the Ambrona sites was compared to other inner Iberian sites as well as to Mediterranean sites. Sediment samples as well as mineral crusts from graves were analysed from the Neolithic tumulus of La Peña de la Abuela. Its diachronic collective burials had originated from a period of time during the first third of the 4th millennium B.C. Probably no crops, but many green vegetative parts of pine, oak, and juniper had been used as funeral gifts. Oak cupula development indicated early summer activities in the grave-mound. Wickerwork made of willow was used for embedding the dead bodies. 相似文献
217.
218.
Clum A Tindall BJ Sikorski J Ivanova N Mavrommatis K Lucas S Glavina T Del Rio Nolan M Chen F Tice H Pitluck S Cheng JF Chertkov O Brettin T Han C Detter JC Kuske C Bruce D Goodwin L Ovchinikova G Pati A Mikhailova N Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Chain P Rohde M Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(3):308-316
Pirellula staleyi Schlesner and Hirsch 1987 is the type species of the genus Pirellula of the family Planctomycetaceae. Members of this pear- or teardrop-shaped bacterium show a clearly visible pointed attachment pole and can be distinguished from other Planctomycetes by a lack of true stalks. Strains closely related to the species have been isolated from fresh and brackish water, as well as from hypersaline lakes. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of the order Planctomyces and only the second sequence from the phylum Planctobacteria/Planctomycetes. The 6,196,199 bp long genome with its 4773 protein-coding and 49 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
219.
Pati A Sikorski J Nolan M Lapidus A Copeland A Glavina Del Rio T Lucas S Chen F Tice H Pitluck S Cheng JF Chertkov O Brettin T Han C Detter JC Kuske C Bruce D Goodwin L Chain P D'haeseleer P Chen A Palaniappan K Ivanova N Mavromatis K Mikhailova N Rohde M Tindall BJ Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP 《Standards in genomic sciences》2009,1(2):141-149
Saccharomonospora viridis (Schuurmans et al. 1956) Nonomurea and Ohara 1971 is the type species of the genus Saccharomonospora which belongs to the family Pseudonocardiaceae. S. viridis is of interest because it is a Gram-negative organism classified among the usually Gram-positive actinomycetes. Members of the species are frequently found in hot compost and hay, and its spores can cause farmer's lung disease, bagassosis, and humidifier fever. Strains of the species S. viridis have been found to metabolize the xenobiotic pentachlorophenol (PCP). The strain described in this study has been isolated from peat-bog in Ireland. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the family Pseudonocardiaceae, and the 4,308,349 bp long single replicon genome with its 3906 protein-coding and 64 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
220.
Labutti K Pukall R Steenblock K Glavina Del Rio T Tice H Copeland A Cheng JF Lucas S Chen F Nolan M Bruce D Goodwin L Pitluck S Ivanova N Mavromatis K Ovchinnikova G Pati A Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Chain P Saunders E Brettin T Detter JC Han C Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(2):159-165
Anaerococcus prevotii (Foubert and Douglas 1948) Ezaki et al. 2001 is the type species of the genus, and is of phylogenetic interest because of its arguable assignment to the provisionally arranged family 'Peptostreptococcaceae'. A. prevotii is an obligate anaerobic coccus, usually arranged in clumps or tetrads. The strain, whose genome is described here, was originally isolated from human plasma; other strains of the species were also isolated from clinical specimen. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the genus. Next to Finegoldia magna, A. prevotii is only the second species from the family 'Peptostreptococcaceae' for which a complete genome sequence is described. The 1,998,633 bp long genome (chromosome and one plasmid) with its 1852 protein-coding and 61 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献