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https://www.readbyqxmd.com/read/28817927/identification-of-biosynthetic-gene-clusters-from-metagenomic-libraries-using-pptase-complementation-in-a-streptomyces-host
#1
J Kipchirchir Bitok, Christophe Lemetre, Melinda A Ternei, Sean F Brady
The majority of environmental bacteria are not readily cultured in the lab, leaving the natural products they make inaccessible using culture-dependent discovery methods. Cloning and heterologous expression of DNA extracted from environmental samples (environmental DNA, eDNA) provides a means of circumventing this discovery bottleneck. To facilitate the identification of clones containing biosynthetic gene clusters, we developed a model heterologous expression reporter strain Streptomyces albus::bpsA ΔPPTase...
September 1, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28812299/conversion-of-the-high-yield-salinomycin-producer-streptomyces-albus-bk3-25-into-a-surrogate-host-for-polyketide-production
#2
Xiaojie Zhang, Chenyang Lu, Linquan Bai
An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization, fast growth, abundant precursors and energy supply, and a pronounced gene expression. Streptomyces albus BK3-25 is a high-yield industrial strain producing type-I polyketide salinomycin, with a unique ability of bean oil utilization. Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein. Firstly, introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and salinomycin, and subsequent deletion of the salinomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors, including malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA...
August 14, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28805296/basidiomycete-specific-pscamkl1-encoding-a-camk-like-protein-kinase-is-required-for-full-virulence-of-puccinia-striiformis-f-sp-tritici
#3
Min Jiao, Dan Yu, Chenglong Tan, Jia Guo, Dingyun Lan, Ershang Han, Tuo Qi, Ralf Thomas Voegele, Zhensheng Kang, Jun Guo
Calcium/calmodulin-dependent kinases (CaMKs) are Ser/Thr protein kinases (PKs) that respond to changes in cytosolic free Ca(2+) and play diverse roles in eukaryotes. In fungi, CAMKs are generally classified into four families CAMK1, CAMKL, RAD53, and CAMK-Unique. Among these, CAMKL constitutes the largest family. In some fungal plant pathogens members of the CaMKL family have been shown to be responsible for pathogenesis. However, little is known about their role(s) in rust fungi. In this study, we functionally characterized a novel PK gene, PsCaMKL1, from Puccinia striiformis f...
August 14, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28783252/the-polyketide-synthase-ospks2-is-essential-for-pollen-exine-and-ubisch-body-patterning-in-rice
#4
Xiaolei Zhu, Jing Yu, Jianxin Shi, Takayuki Tohge, Alisdair R Fernie, Sagit Meir, Asaph Aharoni, Dawei Xu, Dabing Zhang, Wanqi Liang
Lipid and phenolic metabolism are important for pollen exine formation. In Arabidopsis, polyketide synthases (PKSs) are essential for both sporopollenin biosynthesis and exine formation. Here, we characterized the role of a polyketide synthase (OsPKS2) in male reproduction of rice (Oryza sativa). Recombinant OsPKS2 catalyzed the condensation of fatty acyl-CoA with malonyl-CoA to generate triketide and tetraketide α-pyrones, the main components of pollen exine. Indeed, the ospks2 mutant had defective exine patterning and was male sterile...
August 7, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28746914/a-phase-i-clinical-trial-of-binimetinib-in-combination-with-folfox-in-patients-with-advanced-metastatic-colorectal-cancer-who-failed-prior-standard-therapy
#5
May Cho, Jun Gong, Paul Frankel, Timothy W Synold, Dean Lim, Vincent Chung, Joseph Chao, Daneng Li, Yuan Chen, Stephen Sentovich, Kurt Melstrom, Gagandeep Singh, Eloise Luevanos, Marwan Fakih
BACKGROUND: This was a first in-human, open-label, dose-escalation phase I study conducted to evaluate the maximum tolerated dose (MTD), safety, and efficacy of the combination of oral binimetinib and FOLFOX. MATERIALS AND METHODS: Patients with metastatic colorectal cancer (mCRC) who progressed on prior standard therapies received twice daily binimetinib continuously or intermittently with FOLFOX. Dose-limiting toxicities (DLTs) were assessed in the first 2 cycles of study treatment...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745802/progressive-subglottic-stenosis-in-a-child-with-pallister-killian-syndrome
#6
Tadashi Shiohama, Katsunori Fujii, Kenji Shimizu, Hirofumi Ohashi, Tomozumi Takatani, Nobuhiko Okamoto, Gen Nishimura, Mitsuhiro Kato, Naoki Shimojo
Pallister-Killian syndrome (PKS) is rare genetic disorder caused by tetrasomy 12p mosaicism with supernumerary isochromosome 12p that manifests with intellectual disability, craniofacial dysmorphism, and epilepsy. Although PKS presents as a multisystem morphological defect, respiratory system involvement is rare, except for diaphragmatic hernia. We are the first to report a case of PKS with progressive subglottic stenosis. Subglottic stenosis is a potentially lethal condition due to severe respiratory obstruction and difficult intubation; therefore, further accumulation of cases is required to assess the causal link between PKS and subglottic stenosis...
July 26, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28739420/long-term-visual-outcomes-comparing-descemet-stripping-automated-endothelial-keratoplasty-and-penetrating-keratoplasty
#7
Matthias Fuest, Marcus Ang, Hla Myint Htoon, Donald Tan, Jodhbir S Mehta
PURPOSE: To compare 5-year visual acuity and refraction outcome in Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for Fuchs endothelial dystrophy (FED) or bullous keratopathy (BK) in Asian eyes. DESIGN: Prospective interventional case series. METHODS: We analyzed 828 consecutive cases of DSAEK (423) or PK (405) for FED and BK from the Singapore Cornea Transplant Registry performed from 1991 to 2011...
July 21, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28733613/rnai-screening-identifies-trypanosoma-brucei-stress-response-protein-kinases-required-for-survival-in-the-mouse
#8
Fernando Fernandez-Cortes, Tiago D Serafim, Jonathan M Wilkes, Nathaniel G Jones, Ryan Ritchie, Richard McCulloch, Jeremy C Mottram
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732043/investigation-of-horizontal-gene-transfer-of-pathogenicity-islands-in-escherichia-coli-using-next-generation-sequencing
#9
Maxim Messerer, Wolfgang Fischer, Sören Schubert
Horizontal gene transfer (HGT) contributes to the evolution of bacteria. All extraintestinal pathogenic Escherichia coli (ExPEC) harbour pathogenicity islands (PAIs), however relatively little is known about the acquisition of these PAIs. Due to these islands, ExPEC have properties to colonize and invade its hosts efficiently. Even though these PAIs are known to be acquired by HGT, only very few PAIs do carry mobilization and transfer genes required for the transmission by HGT. In this study, we apply for the first time next-generation sequencing (NGS) and in silico analyses in combination with in vitro experiments to decipher the mechanisms of PAI acquisition in ExPEC...
2017: PloS One
https://www.readbyqxmd.com/read/28731630/improved-pks-gene-expression-with-strong-endogenous-promoter-resulted-in-geldanamycin-yield-increase
#10
Xinran Wang, Xinjuan Ning, Qinqin Zhao, Qianjin Kang, Linquan Bai
The type I polyketide geldanamycin is a potent anti-tumor reagent. Its biosynthesis includes three steps: the biosynthesis of precursors, such as 3-amino-5-hydroxybenzoic acid (AHBA), the PKS chain extension, and the post-PKS modifications. According to the genomic and transcriptomic analysis, the PKS chain extension was deduced to be the rate-limiting step for geldanamycin production in Streptomyces hygroscopicus XM201. in order to improve the expression of PKS genes, a strong endogenous promoter 5063p was obtained based on the transcriptomic analysis and XylE enzymatic assay...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28729856/biological-significance-of-marine-actinobacteria-of-east-coast-of-andhra-pradesh-india
#11
Alapati Kavitha, Handanahal S Savithri
An attempt was made to identify actinobacterial strains present in the marine soil of East Coast regions viz., Chirala, Bapatla, and Peddaganjam, Andhra Pradesh; Kanyakumari, Tamil Nadu and Goa, Goa along with the study of their antimicrobial potential. Eight out of 73 actinobacterial strains isolated from these regions showed strong antimicrobial activity against Gram positive bacteria, Gram negative bacteria, and Candida albicans. Molecular identification (16S rRNA analysis) of the eight strains revealed that they belong to Dietzia sp...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28721067/phase-i-dose-escalation-study-of-long-acting-pasireotide-in-patients-with-neuroendocrine-tumors
#12
James C Yao, Jennifer A Chan, Alain C Mita, Madan G Kundu, Karina Hermosillo Reséndiz, Ke Hu, Shoba Ravichandran, Jonathan R Strosberg, Edward M Wolin
This phase I study aimed at determining the maximum tolerated dose (MTD) and characterizing the safety, tolerability, pharmacokinetics (PKs), and efficacy of pasireotide in patients with advanced neuroendocrine tumors (NETs). Patients were enrolled in two phases: dose-escalation phase (to determine the MTD) at a starting dose of 80 mg pasireotide long-acting release (LAR) i.m. followed by a dose-expansion phase (to evaluate safety and prelimi-nary efficacy). Associations between PK/pharmacodynamic parameters and clinical outcomes were evaluated using linear regression analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28719729/synthesis-of-c-glucosylated-octaketide-anthraquinones-in-n-benthamiana-using-a-multispecies-based-biosynthetic-pathway
#13
Johan Andersen-Ranberg, Kenneth Thermann Kongstad, Majse Nafisi, Dan Staerk, Finn Okkels, Uffe Hasbro Mortensen, Birger Lindberg Møller, Rasmus John Normand Frandsen, Rubini Kannangara
Carminic acid is a C-glucosylated octaketide anthraquinone and the main constituent of the natural dye carmine (E120) possessing unique coloring, stability and solubility properties. Despite being used since ancient times, longstanding efforts to elucidate its route of biosynthesis have been unsuccessful. Herein is reported a novel combination of enzymes derived from a plant (Aloe arborescens, Aa), a bacterium (Streptomyces sp R1128, St), and an insect (Dactylopius coccus, Dc) that allows for the biosynthesis of the C-glucosylated anthraquinone, dcII, a precursor for carminic acid...
July 18, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28703757/oil-palm-waste-based-precursors-as-a-renewable-and-economical-carbon-sources-for-the-preparation-of-reduced-graphene-oxide-from-graphene-oxide
#14
Salisu Nasir, Mohd Zobir Hussein, Nor Azah Yusof, Zulkarnain Zainal
Herein, a new approach was proposed to produce reduced graphene oxide (rGO) from graphene oxide (GO) using various oil palm wastes: oil palm leaves (OPL), palm kernel shells (PKS) and empty fruit bunches (EFB). The effect of heating temperature on the formation of graphitic carbon and the yield was examined prior to the GO and rGO synthesis. Carbonization of the starting materials was conducted in a furnace under nitrogen gas for 3 h at temperatures ranging from 400 to 900 °C and a constant heating rate of 10 °C/min...
July 13, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28701150/physiological-roles-of-sigma-factor-sigd-in-corynebacterium-glutamicum
#15
Hironori Taniguchi, Tobias Busche, Thomas Patschkowski, Karsten Niehaus, Miroslav Pátek, Jörn Kalinowski, Volker F Wendisch
BACKGROUND: Sigma factors are one of the components of RNA polymerase holoenzymes, and an essential factor of transcription initiation in bacteria. Corynebacterium glutamicum possesses seven genes coding for sigma factors, most of which have been studied to some detail; however, the role of SigD in transcriptional regulation in C. glutamicum has been mostly unknown. RESULTS: In this work, pleiotropic effects of sigD overexpression at the level of phenotype, transcripts, proteins and metabolites were investigated...
July 12, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28695854/the-putative-polyketide-cyclase-msmeg_0129-from-mycobacterium-smegmatis-purification-crystallization-and-x-ray-crystallographic-analysis
#16
Shuping Zheng, Ying Zhou, Joy Fleming, Yafeng Zhou, Wei Liu, Lijun Bi
Mycobacterium tuberculosis Rv0164 has previously been identified as a human T-cell antigen that induces significant production of IFN-γ in human peripheral blood mononuclear cells. M. smegmatis MSMEG_0129 shares 59% sequence identity with Rv0164. Based on sequence alignment, both proteins are predicted to be members of the cyclase/dehydrase family, which is part of a large group of enzymes referred to as type II polyketide synthases (PKSs). In biosynthetic pathways mediated by type II PKSs, cyclases catalyze the conversion of linear poly-β-ketones to cyclized intermediates...
July 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28694866/strategies-in-megasynthase-engineering-fatty-acid-synthases-fas-as-model-proteins
#17
REVIEW
Manuel Fischer, Martin Grininger
Megasynthases are large multienzyme proteins that produce a plethora of important natural compounds by catalyzing the successive condensation and modification of precursor units. Within the class of megasynthases, polyketide synthases (PKS) are responsible for the production of a large spectrum of bioactive polyketides (PK), which have frequently found their way into therapeutic applications. Rational engineering approaches have been performed during the last 25 years that seek to employ the "assembly-line synthetic concept" of megasynthases in order to deliver new bioactive compounds...
2017: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28694801/the-gata-type-transcription-factor-csm1-regulates-conidiation-and-secondary-metabolism-in-fusarium-fujikuroi
#18
Eva-Maria Niehaus, Julia Schumacher, Immo Burkhardt, Patrick Rabe, Eduard Spitzer, Martin Münsterkötter, Ulrich Güldener, Christian M K Sieber, Jeroen S Dickschat, Bettina Tudzynski
GATA-type transcription factors (TFs) such as the nitrogen regulators AreA and AreB, or the light-responsive TFs WC-1 and WC-2, play global roles in fungal growth and development. The conserved GATA TF NsdD is known as an activator of sexual development and key repressor of conidiation in Aspergillus nidulans, and as light-regulated repressor of macroconidia formation in Botrytis cinerea. In the present study, we functionally characterized the NsdD ortholog in Fusarium fujikuroi, named Csm1. Deletion of this gene resulted in elevated microconidia formation in the wild-type (WT) and restoration of conidiation in the non-sporulating velvet mutant Δvel1 demonstrating that Csm1 also plays a role as repressor of conidiation in F...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28690095/evolution-of-polyketide-synthesis-in-a-dothideomycete-forest-pathogen
#19
I Kutay Ozturk, Pranav Chettri, Pierre-Yves Dupont, Irene Barnes, Rebecca L McDougal, Geromy G Moore, Andre Sim, Rosie E Bradshaw
Fungal secondary metabolites have many important biological roles and some, like the toxic polyketide aflatoxin, have been intensively studied at the genetic level. Complete sets of polyketide synthase (PKS) genes can now be identified in fungal pathogens by whole genome sequencing and studied in order to predict the biosynthetic potential of those fungi. The pine needle pathogen Dothistroma septosporum is predicted to have only three functional PKS genes, a small number for a hemibiotrophic fungus. One of these genes is required for production of dothistromin, a polyketide virulence factor related to aflatoxin, whose biosynthetic genes are dispersed across one chromosome rather than being clustered...
July 6, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28685195/characterization-of-three-pathway-specific-regulators-for-high-production-of-monensin-in-streptomyces-cinnamonensis
#20
Zheng-Kun Tang, Xiao-Mei Li, Ai-Ping Pang, Chun-Yan Lin, Yue Zhang, Jie Zhang, Jianjun Qiao, Guang-Rong Zhao
Monensin, a polyether ionophore antibiotic, is produced by Streptomyces cinnamonensis and worldwide used as a coccidiostat and growth-promoting agent in the field of animal feeding. The monensin biosynthetic gene cluster (mon) has been reported. In this study, the potential functions of three putatively pathway-specific regulators (MonH, MonRI, and MonRII) were clarified. The results from gene inactivation, complementation, and overexpression showed that MonH, MonRI, and MonRII positively regulate monensin production...
August 2017: Applied Microbiology and Biotechnology
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