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L Pelligand, A Soubret, J N King, J Elliott, J P Mochel
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects...
October 22, 2016: CPT: Pharmacometrics & Systems Pharmacology
Hisayuki Komaki, Akira Hosoyama, Natsuko Ichikawa, Yasuhiro Igarashi
Here, we report the draft genome sequence of Bacillus subtilis TP-B0611, which produces the isocoumarin-type compounds bacilosarcin and amicoumacin. The genome encodes three nonribosomal peptide synthetase (NRPS) gene clusters and one hybrid polyketide synthase (PKS)/NRPS gene cluster. The hybrid PKS/NRPS gene cluster was identified to be responsible for the biosynthesis of bacilosarcins and amicoumacins.
October 13, 2016: Genome Announcements
Futoshi Taura, Miu Iijima, Eriko Yamanaka, Hironobu Takahashi, Hiromichi Kenmoku, Haruna Saeki, Satoshi Morimoto, Yoshinori Asakawa, Fumiya Kurosaki, Hiroyuki Morita
Rhododendron dauricum L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was cloned from young leaves of R. dauricum. The primary structure of ORS shared relatively low identities to those of PKSs from other plants, and the active site of ORS had a unique amino acid composition. The bacterially expressed, recombinant ORS accepted acetyl-CoA as the preferable starter substrate, and produced orcinol as the major reaction product, along with four minor products including OSA...
2016: Frontiers in Plant Science
Zifei Xu, Yonghong Chen, Tianyang Song, Zhijun Zeng, Ni Yan, Keqin Zhang, Xuemei Niu
Arthrobotrys oligospora is the first recognized nematode-trapping fungus and by far the most abundant in the environment. Our recent study revealed the polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora involved in the production of many secondary metabolites and the trap formation of the fungus. Here we report that the disruption of two genes in the upstream flanking region of the gene AOL_s00215g283, AOL_s00215g281 and AOL_s00215g282, which putatively encoded one amidohydrolase and one cytochrome P450 monooxygenase, respectively, both resulted in significant nematicidal activity of the cultural broths of the mutants and loss of morphological regulatory arthrosporols...
October 11, 2016: Journal of Agricultural and Food Chemistry
Meredith A Skiba, Andrew P Sikkema, William D Fiers, William H Gerwick, David H Sherman, Courtney C Aldrich, Janet L Smith
Polyketide metabolites produced by modular type I polyketide synthases (PKS) acquire their chemical diversity through the variety of catalytic domains within modules of the pathway. Methyltransferases are among the least characterized of the catalytic domains common to PKS systems. We determined the domain boundaries and characterized the activity of a PKS C-methyltransferase (C-MT) from the curacin A biosynthetic pathway. The C-MT catalyzes S-adenosylmethionine-dependent methyl transfer to the α-position of β-ketoacyl substrates linked to acyl carrier protein (ACP) or a small-molecule analog, but does not act on β-hydroxyacyl substrates or malonyl-ACP...
October 10, 2016: ACS Chemical Biology
Kajal Chakraborty, Bini Thilakan, Vamshi Krishna Raola, Minju Joy
Heterotrophic Bacillus amyloliquefaciens associated with edible red seaweed, Laurenciae papillosa was used to isolate antibacterial polyketide compounds. Antibacterial activity studies integrated with the outcome obtained by polyketide synthetase (pks) coding genes established that seaweed-affiliated bacterial flora had a wide-ranging antibacterial activities and potential natural product diversity, which proved that the bacterium is valuable reservoir of novel bioactive metabolites. Bioactivity-guided isolation of 3-(octahydro-9-isopropyl-2H-benzo[h]chromen-4-yl)-2-methylpropyl benzoate and methyl 8-(2-(benzoyloxy)-ethyl)-hexahydro-4-((E)-pent-2-enyl)-2H-chromene-6-carboxylate of polyketide origin, with activity against human opportunistic food pathogenic microbes, have been isolated from the ethyl acetate extract of B...
March 1, 2017: Food Chemistry
Wei Wei, Shaohua Shu, Wenjun Zhu, Ying Xiong, Fang Peng
Wolfiporia cocos is an edible and medicinal fungus that grows in association with pine trees, and its dried sclerotium, known as Fuling in China, has been used as a traditional medicine in East Asian countries for centuries. Nearly 10% of the traditional Chinese medicinal preparations contain W. cocos. Currently, the commercial production of Fuling is limited because of the lack of pine-based substrate and paucity of knowledge about the sclerotial development of the fungus. Since protein kinase (PKs) play significant roles in the regulation of growth, development, reproduction, and environmental responses in filamentous fungi, the kinome of W...
2016: Frontiers in Microbiology
Marta Maciejewska, Delphine Adam, Loïc Martinet, Aymeric Naômé, Magdalena Całusińska, Philippe Delfosse, Monique Carnol, Hazel A Barton, Marie-Pierre Hayette, Nicolas Smargiasso, Edwin De Pauw, Marc Hanikenne, Denis Baurain, Sébastien Rigali
Moonmilk speleothems of limestone caves host a rich microbiome, among which Actinobacteria represent one of the most abundant phyla. Ancient medical texts reported that moonmilk had therapeutical properties, thereby suggesting that its filamentous endemic actinobacterial population might be a source of natural products useful in human treatment. In this work, a screening approach was undertaken in order to isolate cultivable Actinobacteria from moonmilk of the Grotte des Collemboles in Belgium, to evaluate their taxonomic profile, and to assess their potential in biosynthesis of antimicrobials...
2016: Frontiers in Microbiology
Yu-Rong Cheng, Zhi-Jie Sun, Gu-Zhen Cui, Xiaojin Song, Qiu Cui
Developing a strain with high docosahexaenoic acid (DHA) yield and stable fermenting-performance is an imperative way to improve DHA production using Aurantiochytrium sp., a microorganism with two fatty acid synthesis pathways: polyketide synthase (PKS) pathway and Type I fatty acid synthase (FAS) pathway. This study investigated the growth and metabolism response of Aurantiochytrium sp. CGMCC 6208 to two inhibitors of enoyl-ACP reductase of Type II FAS pathway (isoniazid and triclosan), and proposed a method of screening high DHA yield Aurantiochytrium sp...
November 2016: Enzyme and Microbial Technology
Chris A Dejong, Gregory M Chen, Haoxin Li, Chad W Johnston, Mclean R Edwards, Philip N Rees, Michael A Skinnider, Andrew L H Webster, Nathan A Magarvey
Polyketides (PKs) and nonribosomal peptides (NRPs) are profoundly important natural products, forming the foundations of many therapeutic regimes. Decades of research have revealed over 11,000 PK and NRP structures, and genome sequencing is uncovering new PK and NRP gene clusters at an unprecedented rate. However, only ∼10% of PK and NRPs are currently associated with gene clusters, and it is unclear how many of these orphan gene clusters encode previously isolated molecules. Therefore, to efficiently guide the discovery of new molecules, we must first systematically de-orphan emergent gene clusters from genomes...
October 3, 2016: Nature Chemical Biology
B Urman, S Misirlioglu, H Bengisu, E Turkgeldi, S Aksu, B Ata, O Oktem, C Taskiran
No abstract text is available yet for this article.
November 2015: Journal of Minimally Invasive Gynecology
S Aksu, S Misirlioglu, C Taskiran, B Urman
No abstract text is available yet for this article.
November 2015: Journal of Minimally Invasive Gynecology
Gesche Berkhan, Christian Merten, Claudia Holec, Frank Hahn
The olefin shift is an important modification during polyketide biosynthesis. Particularly for type I cis-AT PKS, little information has been gained on the enzymatic mechanisms involved. We present our in vitro investigations on the olefin shift occurring during ambruticin biosynthesis. The unique, multifunctional domain AmbDH4 catalyzes consecutive dehydration, epimerization, and enoyl isomerization. The resulting 3-enethioate is removed from the equilibrium by α-methylation catalyzed by the highly specific C-methyltransferase AmbM...
October 17, 2016: Angewandte Chemie
Zhuxia Zhang, Jie Yang, Xiaolei Liu, Xiaoe Jia, Shengdi Xu, Kerui Gong, Shaochun Yan, Chunyang Zhang, Guo Shao
BACKGROUND: Learning and memory is a complex process. Some reports have shown that protein kinases (PKs) and phosphatases (PPs) are important mediators in this process. And it is also well known that protein serine/threonine phosphatase 1 (PP1) and DNA methylation are critically involved in learning and memory. METHODS: In the current study, the mice and cultured cells (NG108-15) were treated with vehicle or 5-Aza-2'-deoxycytidine (5-aza-cdR), a DNA methyltransferase (DNMT) inhibitor...
September 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yun-Feng Peng, Wen-Chao Chen, Kang Xiao, Lin Xu, Lian Wang, Xia Wan
The gene encoding phosphopantetheinyl transferase (PPTase), pfaE, a component of the polyketide synthase (PKS) pathway, is crucial for the production of docosahexaenoic acid (DHA, 22:6ω3), along with the other pfa cluster members pfaA, pfaB, pfaC and pfaD. DHA was produced in Escherichia coli by co-expressing pfaABCD from DHA-producing Colwellia psychrerythraea 34H with one of four pfaE genes from bacteria producing arachidonic acid (ARA, 20:4ω6), eicosapentaenoic acid (EPA, 20:5ω3) or DHA, respectively...
2016: PloS One
Sook-Jin Kim, Seo-Hee Heo, Dong-Seok Lee, In Gyun Hwang, Yong-Bok Lee, Hea-Young Cho
The aim of this study was to confirm and investigate the gender differences in pharmacokinetic (PK) characteristics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances (PFASs) consisted of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) in both male and female rats. For this study, a simultaneous determination method of the 3 PFASs in rat plasma and tissues was developed and validated using a UPLC-MS/MS system. The PK parameters after a single oral or intravenous administration of the 3 PFASs in both rats were calculated using WinNonlin(®) software...
September 13, 2016: Food and Chemical Toxicology
Ira Vashisht, Tarun Pal, Hemant Sood, Rajinder S Chauhan
Transcriptional regulation of picrosides biosynthesis, the iridoid glycosides of an endangered medicinal herb, Picrorhiza kurroa, is completely unknown. P. kurroa plants obtained from natural habitat accumulate higher picrosides than in-vitro cultured plants, which necessitates identification of transcription factors (TFs) regulating their differential biosynthesis. The current study investigates complete spectrum of different TF classes in P. kurroa transcriptomes and discerns their association with picrosides biosynthesis...
September 15, 2016: Molecular Biology Reports
Lulu Xie, Pingli Liu, Zhixin Zhu, Shifan Zhang, Shujiang Zhang, Fei Li, Hui Zhang, Guoliang Li, Yunxiao Wei, Rifei Sun
Polyketide synthases (PKSs) utilize the products of primary metabolism to synthesize a wide array of secondary metabolites in both prokaryotic and eukaryotic organisms. PKSs can be grouped into three distinct classes, types I, II, and III, based on enzyme structure, substrate specificity, and catalytic mechanisms. The type III PKS enzymes function as homodimers, and are the only class of PKS that do not require acyl carrier protein. Plant type III PKS enzymes, also known as chalcone synthase (CHS)-like enzymes, are of particular interest due to their functional diversity...
2016: Frontiers in Plant Science
Kajal Chakraborty, Bini Thilakan, Rekha Devi Chakraborty, Vamshi Krishna Raola, Minju Joy
The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B...
September 13, 2016: Applied Microbiology and Biotechnology
Kacey B Anderson, Samuel M Poloyac, Patrick M Kochanek, Philip E Empey
Targeted temperature management (TTM) has been shown to reduce mortality and improve neurological outcomes in out-of-hospital cardiac arrest (CA) patients and in neonates with hypoxic-ischemic encephalopathy (HIE). TTM has also been associated with adverse drug events in the critically ill patient due to its effect on drug pharmacokinetics (PKs) and pharmacodynamics (PDs). We aim to evaluate the current literature on the effect of TTM on drug PKs and PDs following CA. MEDLINE/PubMed databases were searched for publications, which include the MeSH terms hypothermia, drug metabolism, drug transport, P450, critical care, cardiac arrest, hypoxic-ischemic encephalopathy, pharmacokinetics, and pharmacodynamics between July 2006 and October 2015...
September 13, 2016: Therapeutic Hypothermia and Temperature Management
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