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https://www.readbyqxmd.com/read/28330310/diversity-and-bioactive-potentials-of-culturable-heterotrophic-bacteria-from-the-surficial-sediments-of-the-arabian-sea
#1
Abdulaziz Anas, Charulatha Nilayangod, C Jasmin, Saradavey Vinothkumar, P S Parameswaran, Shanta Nair
Marine sediments accommodate plethora of diverse microorganisms with varying ecological functions. In the present study, we isolated bacteria from surficial sediments of south east Arabian Sea (AS) and evaluated their bioactive potentials. A total of 131 isolates belonging to the phylum: γ-Proteobacteria (63%), Bacillales (34%) and Micrococcaceae (3%) were isolated. Among these, about 40% of the isolates showed the presence of secondary metabolite biosynthetic genes such as PKS or NRPS or both. Organic extracts of nearly 50% of these organisms were cytotoxic to human breast cancer MCF-7 cells and were bactericidal to human pathogens, Escherichia coli and Pseudomonas sp...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28326787/linear-peptides-are-the-major-products-of-a-biosynthetic-pathway-that-encodes-for-cyclic-depsipeptides
#2
Thomas P Wyche, Antonio C Ruzzini, Christine Beemelmanns, Ki Hyun Kim, Jonathan L Klassen, Shugeng Cao, Michael Poulsen, Tim S Bugni, Cameron R Currie, Jon Clardy
Three new dentigerumycin analogues are produced by Streptomyces sp. M41, a bacterium isolated from a South African termite, Macrotermes natalensis. The structures of the complex nonribosomal peptide synthetase-polyketide synthase (NRPS/PKS) hybrid compounds were determined by 1D- and 2D-NMR spectroscopy, high-resolution mass spectrometry, and circular dichroism (CD) spectroscopy. Both cyclic and linear peptides are reported, and the genetic organization of the NRPS modules within the biosynthetic gene cluster accounts for the observed structural diversity...
March 22, 2017: Organic Letters
https://www.readbyqxmd.com/read/28323151/a-proteasome-inhibitor-produced-by-burkholderia-pseudomallei-modulates-intracellular-growth
#3
Sariqa Wagley, Muthita Vanaporn, Darawan Rinchai, Laura Conejero, Ganjana Lertmemongkolchai, Gregory J Bancroft, Richard W Titball
The NRPS/PKS cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the Burkholderia genus including B. pseudomallei. In this study we have shown that the insertional inactivation or deletion of glbC in this cluster in B. pseudomallei could reduce the ability of the bacterium to survive or grow in murine macrophages or in human neutrophils. Exogenously added proteasome inhibitors were able to chemically complement the mutation. The insertional inactivation or deletion of glbC increased virulence in an acute model of infection in Balb/c or C57BL/6 mice but virulence in a chronic model of infection was similar to that of the wild type...
March 18, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28316019/population-pharmacokinetic-analysis-of-rebamipide-in-healthy-korean-subjects-with-the-characterization-of-atypical-complex-absorption-kinetics
#4
Lien Ngo, Hee-Doo Yoo, Phuong Tran, Hea-Young Cho, Yong-Bok Lee
In this study, the population pharmacokinetic (PK) analysis of rebamipide (Reba) in healthy male Korean subjects was analyzed using the nonlinear mixed effects modeling method. The possible effects of physiological covariates and the multidrug resistance (MDR1) gene 3435C>T polymorphism on PK parameters were also investigated. Data were collected from a bioequivalence study, in which 26 subjects who participated in the study were administered a single oral dose of 100 mg Reba; only data from the reference formulation were used...
March 18, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28293213/curved-walking-rehabilitation-with-a-rotating-treadmill-in-patients-with-parkinson-s-disease-a-proof-of-concept
#5
Marco Godi, Marica Giardini, Antonio Nardone, Anna Maria Turcato, Marco Caligari, Fabrizio Pisano, Marco Schieppati
Training subjects to step-in-place eyes open on a rotating platform while maintaining a fixed body orientation in space [podokinetic stimulation (PKS)] produces a posteffect consisting in inadvertent turning around while stepping-in-place eyes closed [podokinetic after-rotation (PKAR)]. Since the rationale for rehabilitation of curved walking in Parkinson's disease is not fully known, we tested the hypothesis that repeated PKS favors the production of curved walking in these patients, who are uneasy with turning, even when straight walking is little affected...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28293034/characterization-of-bafilomycin-biosynthesis-in-kitasatospora-setae-km-6054-and-comparative-analysis-of-gene-clusters-in-actinomycetales-microorganisms
#6
Ayako Nara, Takuya Hashimoto, Mamoru Komatsu, Makoto Nishiyama, Tomohisa Kuzuyama, Haruo Ikeda
Bafilomycins A1, C1 and B1 (setamycin) produced by Kitasatospora setae KM-6054 belong to the plecomacrolide family, which exhibit antibacterial, antifungal, antineoplastic and immunosuppressive activities. An analysis of gene clusters from K. setae KM-6054 governing the biosynthesis of bafilomycins revealed that it contains five large open reading frames (ORFs) encoding the multifunctional polypeptides of bafilomycin polyketide synthases (PKSs). These clustered PKS genes, which are responsible for bafilomycin biosynthesis, together encode 11 homologous sets of enzyme activities, each catalyzing a specific round of polyketide chain elongation...
March 15, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28292933/complete-elucidation-of-the-late-steps-of-bafilomycin-biosynthesis-in-streptomyces-lohii
#7
Zhong Li, Lei Du, Wei Zhang, Xingwang Zhang, Yuanyuan Jiang, Kun Liu, Ping Men, Huifang Xu, Jeffrey L Fortman, David H Sherman, Bing Yu, Song Gao, Shengying Li
Bafilomycins are an important subgroup of polyketides with diverse biological activities and possible applications as specific inhibitors of vacuolar H+-ATPase. However, the general toxicity and structural complexity of bafilomycins present formidable challenges to drug design via chemical modification, prompting interests in improving bafilomycin activities via biosynthetic approaches. Two bafilomycin biosynthetic gene clusters have been identified, but their post- polyketide synthase (PKS) tailoring steps for structural diversification and bioactivity improvement remain largely unknown...
March 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28288424/slow-pyrolyzed-biochars-from-crop-residues-for-soil-metal-loid-immobilization-and-microbial-community-abundance-in-contaminated-agricultural-soils
#8
Avanthi Deshani Igalavithana, Jinje Park, Changkook Ryu, Young Han Lee, Yohey Hashimoto, Longbin Huang, Eilhann E Kwon, Yong Sik Ok, Sang Soo Lee
This study evaluated the feasibility of using biochars produced from three types of crop residues for immobilizing Pb and As and their effects on the abundance of microbial community in contaminated lowland paddy (P-soil) and upland (U-soil) agricultural soils. Biochars were produced from umbrella tree [Maesopsis eminii] wood bark [WB], cocopeat [CP], and palm kernel shell [PKS] at 500 °C by slow pyrolysis at a heating rate of 10 °C min(-1). Soils were incubated with 5% (w w(-1)) biochars at 25 °C and 70% water holding capacity for 45 d...
March 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28283327/pharmacokinetics-of-perfluorobutane-after-intra-venous-bolus-injection-of-sonazoid-in-healthy-chinese-volunteers
#9
Pengfei Li, Susan Hoppmann, Ping Du, Huiling Li, Paul M Evans, Siver A Moestue, Weiyue Yu, Fang Dong, Hongchuan Liu, Lihong Liu
Sonazoid is an ultrasound contrast agent based on microbubbles (MB) containing perfluorobutane (PFB) gas. Sonazoid is approved in Japan, Korea and Norway for contrast-enhanced ultrasonography of focal liver lesions and focal breast lesions (Japan only). The objective of this study was to determine the pharmacokinetics (PKs) and safety of Sonazoid in Chinese healthy volunteers (HVs) and to evaluate the potential for ethnic differences in PKs between Chinese and Caucasian HVs. Sonazoid was administered as an intra-venous bolus injection at the clinical dose of 0...
March 7, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28271063/pharmacokinetics-of-standard-and-reduced-dose-recombinant-human-soluble-thrombomodulin-in-patients-with-septic-disseminated-intravascular-coagulation-during-continuous-hemodiafiltration
#10
Eizo Watanabe, Shingo Yamazaki, Daisuke Setoguchi, Tomohito Sadahiro, Yoshihisa Tateishi, Tatsuya Suzuki, Itsuko Ishii, Shigeto Oda
INTRODUCTION: Recombinant human soluble thrombomodulin (rTM) is reportedly excreted by the kidneys; therefore, the recommended dose for patients with renal impairment is one-third of the standard dose. The aim of this study was to evaluate whether this reduced dose of rTM achieves effective drug concentrations that are comparable to those of the standard dose in treating sepsis-induced disseminated intravascular coagulation (DIC) during continuous hemodiafiltration (CHDF). METHODS: Eight patients in an intensive care unit were randomized to receive either reduced-dose (0...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28270798/wide-distribution-of-foxicin-biosynthetic-gene-clusters-in-streptomyces-strains-an-unusual-secondary-metabolite-with-various-properties
#11
Anja Greule, Marija Marolt, Denise Deubel, Iris Peintner, Songya Zhang, Claudia Jessen-Trefzer, Christian De Ford, Sabrina Burschel, Shu-Ming Li, Thorsten Friedrich, Irmgard Merfort, Steffen Lüdeke, Philippe Bisel, Michael Müller, Thomas Paululat, Andreas Bechthold
Streptomyces diastatochromogenes Tü6028 is known to produce the polyketide antibiotic polyketomycin. The deletion of the pokOIV oxygenase gene led to a non-polyketomycin-producing mutant. Instead, novel compounds were produced by the mutant, which have not been detected before in the wild type strain. Four different compounds were identified and named foxicins A-D. Foxicin A was isolated and its structure was elucidated as an unusual nitrogen-containing quinone derivative using various spectroscopic methods...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28268063/human-escherichia-coli-isolates-from-hemocultures-septicemia-linked-to-urogenital-tract-infections-is-caused-by-isolates-harboring-more-virulence-genes-than-bacteraemia-linked-to-other-conditions
#12
Lenka Micenková, Alžbeta Beňová, Lucia Frankovičová, Juraj Bosák, Martin Vrba, Alena Ševčíková, Marta Kmeťová, David Šmajs
Escherichia coli is the most common cause of bloodstream infections and community-acquired sepsis. The main aim of this study was to determine virulence characteristics of E. coli isolates from hemocultures of patients with a primary disease of urogenital tract, digestive system, a neoplastic blood disease, or other conditions. Results from a set of 314 E. coli isolates from hemocultures were compared to data from a previously published analysis of 1283 fecal commensal E. coli isolates. Genetic profiling of the 314 E...
February 27, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28245269/chemogenomics-driven-discovery-of-endogenous-polyketide-anti-infective-compounds-from-endosymbiotic-emericella-variecolor-clb38-and-their-rna-secondary-structure-analysis
#13
H C Yashavantha Rao, Devaraju Rakshith, Ballagere Puttaraju Harini, Doddahosuru Mahadevappa Gurudatt, Sreedharamurthy Satish
In the postgenomic era, a new strategy for chemical dereplication of polyketide anti-infective drugs requires novel genomics and chromatographic strategies. An endosymbiotic fungal strain CLB38 was isolated from the root tissue of Combretum latifolium Blume (Combretaceae) which was collected from the Western Ghats of India. The isolate CLB38 was then identified as Emericella variecolor by its characteristic stellate ascospores culture morphology and molecular analysis of ITS nuclear rDNA and intervening 5.8S rRNA gene sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28240912/domain-targeted-metabolomics-delineates-the-heterocycle-assembly-steps-of-colibactin-biosynthesis
#14
Eric P Trautman, Alan R Healy, Emilee E Shine, Seth B Herzon, Jason M Crawford
Modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) comprise giant multidomain enzymes responsible for the "assembly line" biosynthesis of many genetically encoded small molecules. Site-directed mutagenesis, protein biochemical, and structural studies have focused on elucidating the catalytic mechanisms of individual multidomain proteins and protein domains within these megasynthases. However, probing their functions at the cellular level typically has invoked the complete deletion (or overexpression) of multidomain-encoding genes or combinations of genes and comparing those mutants with a control pathway...
March 10, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28239372/identification-by-genome-mining-of-a-type-i-polyketide-gene-cluster-from-streptomyces-argillaceus-involved-in-the-biosynthesis-of-pyridine-and-piperidine-alkaloids-argimycins-p
#15
Suhui Ye, Brian Molloy, Alfredo F Braña, Daniel Zabala, Carlos Olano, Jesús Cortés, Francisco Morís, José A Salas, Carmen Méndez
Genome mining of the mithramycin producer Streptomyces argillaceus ATCC 12956 revealed 31 gene clusters for the biosynthesis of secondary metabolites, and allowed to predict the encoded products for 11 of these clusters. Cluster 18 (renamed cluster arp) corresponded to a type I polyketide gene cluster related to the previously described coelimycin P1 and streptazone gene clusters. The arp cluster consists of fourteen genes, including genes coding for putative regulatory proteins (a SARP-like transcriptional activator and a TetR-like transcriptional repressor), genes coding for structural proteins (three PKSs, one aminotransferase, two dehydrogenases, two cyclases, one imine reductase, a type II thioesterase, and a flavin reductase), and one gene coding for a hypothetical protein...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28238725/functional-and-structural-analysis-of-programmed-c-methylation-in-the-biosynthesis-of-the-fungal-polyketide-citrinin
#16
Philip A Storm, Dominik A Herbst, Timm Maier, Craig A Townsend
Fungal polyketide synthases (PKSs) are large, multidomain enzymes that biosynthesize a wide range of natural products. A hallmark of these megasynthases is the iterative use of catalytic domains to extend and modify a series of enzyme-bound intermediates. A subset of these iterative PKSs (iPKSs) contains a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework. Neither the basis by which only specific positions on the growing intermediate are methylated ("programming") nor the mechanism of methylation are well understood...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28229977/non-ribosomal-peptide-synthetases-identifying-the-cryptic-gene-clusters-and-decoding-the-natural-product
#17
REVIEW
Mangal Singh, Sandeep Chaudhary, Dipti Sareen
Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) present in bacteria and fungi are the major multi-modular enzyme complexes which synthesize secondary metabolites like the pharmacologically important antibiotics and siderophores. Each of the multiple modules of an NRPS activates a different amino or aryl acid, followed by their condensation to synthesize a linear or cyclic natural product. The studies on NRPS domains, the knowledge of their gene cluster architecture and tailoring enzymes have helped in the in silico genetic screening of the ever-expanding sequenced microbial genomic data for the identification of novel NRPS/PKS clusters and thus deciphering novel non-ribosomal peptides (NRPs)...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28223378/population-pharmacokinetic-analysis-of-doripenem-after-intravenous-infusion-in-korean-patients-with-acute-infections
#18
Dong-Hwan Lee, Yong Kyun Kim, Kyubok Jin, Myoung Joo Kang, Young-Don Joo, Yang Wook Kim, Young Soo Moon, Jae-Gook Shin, Sungmin Kiem
We investigated population pharmacokinetics (PK) of doripenem in Korean patients with acute infections, and determined an appropriate dosing regimen using a Monte-Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20∼50 mL/min or >50 mL/min who received a 250-mg or 500-mg dose of doripenem over the course of one hour every eight hours, respectively, were included in this study. Blood samples were taken pre-dose and 0 h, 0.5 h, and 4-6 h after the fourth infusion...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28218912/engineering-fatty-acid-synthases-for-directed-polyketide-production
#19
Jan Gajewski, Floris Buelens, Sascha Serdjukow, Melanie Janßen, Niña Cortina, Helmut Grubmüller, Martin Grininger
In this study, we engineered fatty acid synthases (FAS) for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach. Along with exploring the synthetic capability of FAS, we aim to build a foundation for efficient protein engineering, with the specific goal of harnessing evolutionarily related megadalton-scale polyketide synthases (PKS) for the tailored production of bioactive natural compounds.
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28215351/a-genomic-comparison-of-putative-pathogenicity-related-gene-families-in-five-members-of-the-ophiostomatales-with-different-lifestyles
#20
Ljerka Lah, Ulrike Löber, Tom Hsiang, Stefanie Hartmann
Ophiostomatoid fungi are vectored by their bark-beetle associates and colonize different host tree species. To survive and proliferate in the host, they have evolved mechanisms for detoxification and elimination of host defence compounds, efficient nutrient sequestration, and, in pathogenic species, virulence towards plants. Here, we assembled a draft genome of the spruce pathogen Ophiostoma bicolor. For our comparative and phylogenetic analyses, we mined the genomes of closely related species (Ophiostoma piceae, Ophiostoma ulmi, Ophiostoma novo-ulmi, and Grosmannia clavigera)...
March 2017: Fungal Biology
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