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https://www.readbyqxmd.com/read/30023706/fd5180-a-novel-protein-kinase-affinity-probe-and-the-effect-of-bead-loading-on-protein-kinase-identification
#1
Fiona M Deane, Andrew J S Lin, Peter G Hains, Sarah L Pilgrim, Phillip J Robinson, Adam McCluskey
The effects of compound loading on the identification of protein kinases (PKs) was examined using two previously reported sepharose-supported PK inhibitors (PKIs): bisindolylmaleimide X ( S1 ) and CZC8004 ( S2 ). Compound loadings of 0.1, 0.5, 2.5, 5, 10, 25, and 50% content and an ethanolamine-blocked control bead (no compound) were investigated. A 50% bead loading gave the highest level of PK identification for both S1 and S2 , extracting 34 and 55 PKs, respectively, from a single cell lysate. Control beads allowed overall identification of 23 PKs, which we term the kinase beadome, whereas sepharose-supported sunitinib ( S7 ; 50% loading) identified 20, 11 of which were common to the control beads...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/30022224/a-phase-i-pharmacokinetic-and-pharmacodynamic-study-of-gti-2040-in-combination-with-gemcitabine-in-patients-with-solid-tumors
#2
Laeeq Malik, Anthony Zwiebel, James Cooper
PURPOSE: GTI-2040 is a novel antisense oligonucleotide inhibitor of the R2 subunit of ribonucleotide reductase. This phase I study assessed safety and maximum tolerated dose (MTD) of GTI-2040 in combination with weekly gemcitabine in patients with advanced solid tumors. METHODS: GTI-2040 was given as a 14-day continuous intravenous infusion, while gemcitabine was administered on days 1, 8, and 15. This combination was repeated every 4 weeks and study followed a modified 3 + 3 Fibonacci schema...
July 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30022008/acyltransferases-as-tools-for-polyketide-synthase-engineering
#3
REVIEW
Ewa Maria Musiol-Kroll, Wolfgang Wohlleben
Polyketides belong to the most valuable natural products, including diverse bioactive compounds, such as antibiotics, anticancer drugs, antifungal agents, immunosuppressants and others. Their structures are assembled by polyketide synthases (PKSs). Modular PKSs are composed of modules, which involve sets of domains catalysing the stepwise polyketide biosynthesis. The acyltransferase (AT) domains and their "partners", the acyl carrier proteins (ACPs), thereby play an essential role. The AT loads the building blocks onto the "substrate acceptor", the ACP...
July 18, 2018: Antibiotics
https://www.readbyqxmd.com/read/30020937/identification-of-a-putative-polyketide-synthase-gene-involved-in-usnic-acid-biosynthesis-in-the-lichen-nephromopsis-pallescens
#4
Yi Wang, Changan Geng, Xiaolong Yuan, Mei Hua, Fenghua Tian, Changtian Li
Usnic acid is a unique polyketide produced by lichens. To characterize usnic acid biosynthesis, the transcriptome of the usnic-acid-producing lichen-forming fungus Nephromopsis pallescens was sequenced using Illumina NextSeq technology. Seven complete non-reducing polyketide synthase genes and nine highly-reducing polyketide synthase genes were obtained through transcriptome analysis. Gene expression results obtained by qPCR and usnic acid detection with LCMS-IT-TOF showed that Nppks7 is probably involved in usnic acid biosynthesis in N...
2018: PloS One
https://www.readbyqxmd.com/read/30018826/investigations-into-isoniazid-treated-mycobacterium-tuberculosis-by-electrospray-mass-spectrometry-reveals-new-insights-into-its-lipid-composition
#5
Rahul Pal, Saif Hameed, Varatharajan Sabareesh, Parveen Kumar, Sarman Singh, Zeeshan Fatima
Many of the earlier studies involving the effect of isoniazid (INH) treatment have solely focused on the fatty acyl (FA) category of Mycobacterium tuberculosis (MTB) lipids. This motivated us with the major interest to examine the impact of INH on various other categories of MTB lipids. Towards this, we chose to interpret our mass spectral data (LC-ESI-MS) by a standalone software, MS-LAMP, in which "Mtb LipidDB" was integrated. Analysis by MS-LAMP revealed that INH treatment can alter the composition of "glycerolipids (GLs)" and "glycerophospholipids (GPLs)" categories of MTB lipids, in addition to the variations to FA category...
2018: Journal of Pathogens
https://www.readbyqxmd.com/read/30016947/comparative-analysis-reveals-unexpected-genome-features-of-newly-isolated-thraustochytrids-strains-on-ecological-function-and-pufas-biosynthesis
#6
Zhiquan Song, Jason E Stajich, Yunxuan Xie, Xianhua Liu, Yaodong He, Jinfeng Chen, Glenn R Hicks, Guangyi Wang
BACKGROUND: Thraustochytrids are unicellular fungal-like marine protists with ubiquitous existence in marine environments. They are well-known for their ability to produce high-valued omega-3 polyunsaturated fatty acids (ω-3-PUFAs) (e.g., docosahexaenoic acid (DHA)) and hydrolytic enzymes. Thraustochytrid biomass has been estimated to surpass that of bacterioplankton in both coastal and oceanic waters indicating they have an important role in microbial food-web. Nevertheless, the molecular pathway and regulatory network for PUFAs production and the molecular mechanisms underlying ecological functions of thraustochytrids remain largely unknown...
July 17, 2018: BMC Genomics
https://www.readbyqxmd.com/read/30013270/new-insights-on-cyclization-specificity-of-fungal-type-iii-polyketide-synthase-pksiii-nc-in-neurospora-crassa
#7
Amreesh Parvez, Samir Giri, Renu Bisht, Priti Saxena
Type III polyketide synthases (PKSs) biosynthesize varied classes of metabolites with diverse bio-functionalities. Inherent promiscuous substrate specificity, multiple elongations of reaction intermediates and several modes of ring-closure, confer the proteins with the ability to generate unique scaffolds from limited substrate pools. Structural studies have identified crucial amino acid residues that dictate type III PKS functioning, though cyclization specific residues need further investigation. PKSIII Nc , a functionally and structurally characterized type III PKS from the fungus, Neurospora crassa, is known to biosynthesize alkyl-resorcinol, alkyl-triketide- and alkyl-tetraketide-α-pyrone products...
September 2018: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/30012621/monovalent-ions-modulate-the-flux-through-multiple-folding-pathways-of-an-rna-pseudoknot
#8
Jorjethe Roca, Naoto Hori, Saroj Baral, Yogambigai Velmurugu, Ranjani Narayanan, Prasanth Narayanan, D Thirumalai, Anjum Ansari
The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability, and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine laser temperature-jump experiments and coarse-grained simulations to determine the folding/unfolding pathways of VPK, a variant of the mouse mammary tumor virus (MMTV) PK involved in ribosomal frameshifting...
July 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30007436/lichen-ketosynthase-domains-are-not-responsible-for-inoperative-polyketide-synthases-in-ascomycota-hosts
#9
Mona E Abdel-Hameed, Robert L Bertrand, Lynda J Donald, John L Sorensen
Efforts by lichenologists to characterize lichen polyketide synthases (PKS) through heterologous expression experiments have so far proved unfruitful. A determination of systematic causes of failure is therefore required. Three hypotheses involving the ketosynthase (KS) domain of lichen polyketide synthases (PKS) from Cladonia uncialis are tested: (1) Horizontal versus vertical gene transfer; (2) Typical versus atypical active site residues; (3) Typical versus atypical tertiary protein structure and active site architecture...
July 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30005805/a-closely-related-clade-of-globally-distributed-bloom-forming-cyanobacteria-within-the-nostocales
#10
Connor B Driscoll, Kevin A Meyer, Sigitas Šulčius, Nathan M Brown, Gregory J Dick, Huansheng Cao, Giedrius Gasiūnas, Albertas Timinskas, Yanbin Yin, Zachary C Landry, Timothy G Otten, Timothy W Davis, Susan B Watson, Theo W Dreher
In order to better understand the relationships among current Nostocales cyanobacterial blooms, eight genomes were sequenced from cultured isolates or from environmental metagenomes of recent planktonic Nostocales blooms. Phylogenomic analysis of publicly available sequences placed the new genomes among a group of 15 genomes from four continents in a distinct ADA clade (Anabaena/Dolichospermum/Aphanizomenon) within the Nostocales. This clade contains four species-level groups, two of which include members with both Anabaena-like and Aphanizomenon flos-aquae-like morphology...
July 2018: Harmful Algae
https://www.readbyqxmd.com/read/29997754/culturable-rare-actinomycetes-from-indian-forest-soils-molecular-and-physicochemical-screening-for-biosynthetic-genes
#11
Sunita Bundale, Jaya Singh, Deovrat Begde, Nandita Nashikkar, Avinash Upadhyay
Background and Objectives: Rare actinomycetes are a promising source of novel metabolites of pharmaceutical importance. The current study focussed on selective isolation of specific genera of rare actinomycetes and screening the isolates for biosynthetic genes particularly polyketide synthases (PKS) and non ribosomal peptide synthetases (NRPS). Materials and Methods: The soil samples were subjected to various pre-treatments like 1.5% phenol treatment, 0.3% chloramine T treatment, benzethonium chloride treatment, etc...
April 2018: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/29985125/genetic-diversity-mobilisation-and-spread-of-the-yersiniabactin-encoding-mobile-element-icekp-in-klebsiella-pneumoniae-populations
#12
Margaret M C Lam, Ryan R Wick, Kelly L Wyres, Claire L Gorrie, Louise M Judd, Adam W J Jenney, Sylvain Brisse, Kathryn E Holt
Mobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria's ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in the opportunistic pathogen Klebsiella pneumoniae, which is a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants in K. pneumoniae include the polyketide synthesis loci ybt and clb (also known as pks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin, respectively...
July 9, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29985105/characterization-and-abolishment-of-the-cyclopiazonic-acids-produced-by-aspergillus-oryzae-hmp-f28
#13
Ting Cao, Junhong Ling, Yi Liu, Xiaoqi Chen, Xiaoyue Tian, Dali Meng, Huaqi Pan, Jiangchun Hu, Nan Wang
Extracellular alkalinization and H2 O2 production are important early events during induced resistance establishment in plants. In a screen for metabolites as plant resistance activators from 98 fungal isolates associated with marine sponge Hymeniacidon perleve, the cyclopiazonic acids (CPAs) produced by Aspergillus oryzae HMP-F28 induced significant extracellular alkalinization coupled with augmented H2 O2 production in tobacco cell suspensions. Bioassay-guided fractionation led to the isolation and structural elucidation of a new CPA congener (4, 3-hydroxysperadine A) and three known ones (1-3)...
July 9, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29981902/unexplored-deep-sea-habitats-in-active-volcanic-barren-island-andaman-and-nicobar-islands-are-sources-of-novel-halophilic-eubacteria
#14
Anburajan Lawrance, Meena Balakrishnan, Rajaprabhu Gunasekaran, Rajaguru Srinivasan, Vinithkumar Nambali Valsalan, Dharani Gopal, Kirubagaran Ramalingam
Deep Sea sediment cores were collected from the surrounding of active volcanic Barren Island, Andaman & Nicobar Islands. A total of 24 halophilic eubacteria were isolated and identified based on their biochemical and 16S rDNA sequences. Three major classes (Gamma-Proteobacteria, Alpha-Proteobacteria and Bacilli) of bacteria were detected in the deep sea sediments of active volcanic Barren Island. Among those, 37% of isolates exhibited antimicrobial activity against all tested Gram positive and Gram negative clinical pathogens...
July 5, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29979567/directed-accumulation-of-anticancer-depsipeptides-by-characterization-of-neoantimycins-biosynthetic-pathway-and-an-nadph-dependent-reductase
#15
Yongjun Zhou, Xiao Lin, Simon R Williams, Liyun Liu, Yaoyao Shen, Shu-Ping Wang, Fan Sun, Shihai Xu, Hai Deng, Peter F Leadlay, Hou-Wen Lin
Neoantimycins (NATs) are members of antimycin-type of depsipeptides with outstanding anticancer activities. We isolated NAT-A (1) and -F (2) from the fermentation extract of Streptomyces conglobatus. The NAT biosynthetic gene cluster (nat BGC) was identified by genome sequencing and bioinformatics analysis. nat BGC includes two nonribosomal peptide synthetases (NRPSs) and one polyketide synthase (PKS) genes, and a gene cassette (ten genes), of which the encoded enzymes share high homologs to the ones responsible for 3-formamidosalicylate (3-FAS) biosynthesis in antimycin biosynthetic pathway...
July 6, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29976061/synthetic-pathway-for-the-production-of-olivetolic-acid-in-escherichia-coli
#16
Zaigao Tan, James M Clomburg, Ramon Gonzalez
Type III polyketide synthases (PKS IIIs) contribute to the synthesis of many economically important natural products, most of which are currently produced by direct extraction from plants or through chemical synthesis. Olivetolic acid (OLA) is a plant secondary metabolite sourced from PKS III catalysis, which along with its prenylated derivatives has various pharmacological activities. To demonstrate the potential for microbial cell factories to circumvent limitations of plant extraction or chemical synthesis for OLA, here we utilize a synthetic approach to engineer Escherichia coli for the production of OLA...
July 17, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29969286/selective-actionable-and-druggable-protein-kinases-drive-the-progression-of-neuroendocrine-prostate-cancer
#17
Chao Lu, Yunkai Qie, Shenglai Liu, Changli Wu, Zhihong Zhang, Ranlu Liu, Kuo Yang, Hailong Hu, Yong Xu
Current clinical anti-androgen therapies in advanced prostate cancer (PCa) are driving an increased incidence of neuroendocrine prostate cancer (NEPC), a histological variant exhibiting reduced androgen receptor levels and expression of neuroendocrine markers. The mechanisms underlying the development of NEPC are poorly understood. A set of available data from a well-validated xenograft model of NEPC was used to analyze the exact role of protein kinase (PK) played in the development of NEPC. Fifty-four actionable and druggable PKs, mainly enriched in PI3K-Akt, mTOR, and MAPK signaling pathways, were screened out from the drastically changed PKs during NEPC transdifferentiation...
July 3, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29967601/isolation-diversity-and-antimicrobial-and-immunomodulatory-activities-of-endophytic-actinobacteria-from-tea-cultivars-zijuan-and-yunkang-10-camellia-sinensis-var-assamica
#18
Wei Wei, Yu Zhou, Fanjie Chen, Xiaomei Yan, Yongmin Lai, Chaoling Wei, Xiaoyun Chen, Junfeng Xu, Xu Wang
Endophytic actinobacteria exist widely in plant tissues and are considered as a potential bioresource library of natural products. Tea plants play important roles in human health and in the lifestyles of Asians, especially the Chinese. However, little is known about the endophytic actinobacteria of tea plants. In this study, 16 actinobacteria of 7 different genera and 28 actinobacteria of 8 genera were isolated and analyzed by 16S rRNA gene sequencing from tea cultivars of Zijuan and Yunkang-10 ( Camellia sinensis var...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29958422/lysoquinone-th1-a-new-polyphenolic-tridecaketide-produced-by-expressing-the-lysolipin-minimal-pks-ii-in-streptomyces-albus
#19
Torben Hofeditz, Claudia Eva-Maria Unsin, Jutta Wiese, Johannes F Imhoff, Wolfgang Wohlleben, Stephanie Grond, Tilmann Weber
The structural repertoire of bioactive naphthacene quinones is expanded by engineering Streptomyces albus to express the lysolipin minimal polyketide synthase II (PKS II) genes from Streptomyces tendae Tü 4042 ( llpD-F ) with the corresponding cyclase genes llpCI-CIII . Fermentation of the recombinant strain revealed the two new polyaromatic tridecaketides lysoquinone-TH1 ( 7 , identified) and TH2 ( 8 , postulated structure) as engineered congeners of the dodecaketide lysolipin ( 1 ). The chemical structure of 7 , a benzo[a]naphthacene-8,13-dione, was elucidated by NMR and HR-MS and confirmed by feeding experiments with [1,2-13 C₂]-labeled acetate...
June 28, 2018: Antibiotics
https://www.readbyqxmd.com/read/29958281/duplication-of-a-pks-gene-cluster-and-subsequent-functional-diversification-facilitate-environmental-adaptation-in-metarhizium-species
#20
Guohong Zeng, Peng Zhang, Qiangqiang Zhang, Hong Zhao, Zixin Li, Xing Zhang, Chengshu Wang, Wen-Bing Yin, Weiguo Fang
The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection...
June 29, 2018: PLoS Genetics
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