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https://www.readbyqxmd.com/read/29328619/characterization-of-the-polyspecific-transferase-of-murine-type-i-fatty-acid-synthase-fas-and-implications-for-polyketide-synthase-pks-engineering
#1
Alexander Rittner, Karthik S Paithankar, Khanh Vu Huu, Martin Grininger
Fatty acid synthases (FASs) and polyketide synthases (PKSs) condense acyl compounds to fatty acids and polyketides, respectively. Both, FASs and PKSs, harbor acyltransferases (ATs), which select substrates for condensation by β-ketoacyl synthases (KSs). Here, we present the structural and functional characterization of the polyspecific malonyl/acetyltransferase (MAT) of murine FAS. We assign kinetic constants for the transacylation of the native substrates, acetyl- and malonyl-CoA, and demonstrate the promiscuity of FAS to accept structurally and chemically diverse CoA-esters...
January 12, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29326490/investigation-of-in-vitro-absorption-distribution-metabolism-and-excretion-and-in-vivo-pharmacokinetics-of-paromomycin-influence-on-oral-bioavailability
#2
M Jakir S K Pinjari, Rahul Somani, Ritu M Gilhotra
OBJECTIVE: The objective of this study is to investigate in vitro Caco2 permeability, metabolism and in vivo pharmacokinetic (PK) properties of paromomycin to develop an efficient dosage form with improved oral bioavailability. MATERIALS AND METHODS: For the purpose, Caco2 permeability assay, mouse microsomal stability assay and in vivo PKs in male BALB/c mice were performed. RESULTS: In Caco-2 permeability assay, paromomycin showed negligible permeability in the apical to basolateral (A-to-B) direction and vice versa (B-to-A)...
July 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29324854/characterization-of-the-biosynthetic-gene-cluster-for-cryptic-phthoxazolin-a-in-streptomyces-avermitilis
#3
Dian Anggraini Suroto, Shigeru Kitani, Masayoshi Arai, Haruo Ikeda, Takuya Nihira
Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S. avermitilis is publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is apparent in the sequence data. Here, we identified and characterized the phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing, comparative genomic analysis, and gene disruption...
2018: PloS One
https://www.readbyqxmd.com/read/29323202/genome-based-classification-of-micromonosporae-with-a-focus-on-their-biotechnological-and-ecological-potential
#4
Lorena Carro, Imen Nouioui, Vartul Sangal, Jan P Meier-Kolthoff, Martha E Trujillo, Maria Del Carmen Montero-Calasanz, Nevzat Sahin, Darren Lee Smith, Kristi E Kim, Paul Peluso, Shweta Deshpande, Tanja Woyke, Nicole Shapiro, Nikos C Kyrpides, Hans-Peter Klenk, Markus Göker, Michael Goodfellow
There is a need to clarify relationships within the actinobacterial genus Micromonospora, the type genus of the family Micromonosporaceae, given its biotechnological and ecological importance. Here, draft genomes of 40 Micromonospora type strains and two non-type strains are made available through the Genomic Encyclopedia of Bacteria and Archaea project and used to generate a phylogenomic tree which showed they could be assigned to well supported phyletic lines that were not evident in corresponding trees based on single and concatenated sequences of conserved genes...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318196/engineered-polyketides-synergy-between-protein-and-host-level-engineering
#5
REVIEW
Jesus F Barajas, Jacquelyn M Blake-Hedges, Constance B Bailey, Samuel Curran, Jay D Keasling
Metabolic engineering efforts toward rewiring metabolism of cells to produce new compounds often require the utilization of non-native enzymatic machinery that is capable of producing a broad range of chemical functionalities. Polyketides encompass one of the largest classes of chemically diverse natural products. With thousands of known polyketides, modular polyketide synthases (PKSs) share a particularly attractive biosynthetic logic for generating chemical diversity. The engineering of modular PKSs could open access to the deliberate production of both existing and novel compounds...
September 2017: Synthetic and Systems Biotechnology
https://www.readbyqxmd.com/read/29314577/identification-of-the-biosynthetic-gene-cluster-for-himeic-acid-a-a-ubiquitin-activating-enzyme-e1-inhibitor-in-aspergillus-japonicus-mf275
#6
Makoto Hashimoto, Hikaru Kato, Ayako Katsuki, Sachiko Tsukamoto, Isao Fujii
Himeic acid A, produced by the marine fungus Aspergillus japonicus MF275, is a specific inhibitor of the ubiquitin-activating enzyme E1 in the ubiquitin-proteasome system. To elucidate the mechanism of himeic acid biosynthesis, we first carried out feeding experiments with labeled precursors. The long fatty acyl side chain attached to the pyrone ring was confirmed to be of polyketide origin, while the amide substituent was found to be derived from leucine. These results suggest that a polyketide synthase-non-ribosomal peptide synthase (PKS-NRPS) is involved in himeic acid biosynthesis...
January 5, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29313335/post-polyketide-synthase-carbon-carbon-bond-formation-in-type-ii-pks-derived-natural-products-from-streptomyces-venezuelae
#7
Andrew William Robertson, Jeanna M MacLeod, Logan W MacIntyre, Stephanie M Forget, Steven R Hall, Leah G Bennett, Hebelin Correa, Russell G Kerr, Kerry B Goralski, David L Jakeman
Polyketide synthase (PKS) derived natural products are biosynthesized by head-to-tail addition of acetate and malonate extender units resulting in linear extended-polyketide chains. Despite the well documented structural diversity associated with PKS derived natural products, C-C chain branching deviating from the usual linear pattern is relatively rare. Herein, type-II PKS angucyclic natural products containing a hemiaminal functionality were identified and proposed as the parent of a series of C-C branched analogues...
January 9, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29306326/polyketide-synthases-of-diaporthe-helianthi-and-involvement-of-dhpks1-in-virulence-on-sunflower
#8
Michelina Ruocco, Riccardo Baroncelli, Santa Olga Cacciola, Catello Pane, Maurilia Maria Monti, Giuseppe Firrao, Mariarosaria Vergara, Gaetano Magnano di San Lio, Giovanni Vannacci, Felice Scala
BACKGROUND: The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D...
January 6, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29297422/steady-state-pharmacokinetics-of-cycloserine-in-patients-on-terizidone-for-multidrug-resistant-tuberculosis
#9
R Court, L Wiesner, A Stewart, N de Vries, J Harding, G Maartens, T Gumbo, H McIlleron
SETTING: Terizidone/cycloserine (TRD/CS) is included in standard treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in many countries. The steady state pharmacokinetics (PKs) of CS after TRD administration are not known. OBJECTIVES AND DESIGN: We recruited in-patients treated with 250-750 mg oral TRD daily as part of standard treatment regimens for pulmonary MDR-TB in Cape Town, South Africa. Plasma CS assays were performed in samples taken pre-dose and at 2, 4, 6, 8 and 10 h post-dose...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29289495/mechanism-of-action-pharmacokinetics-efficacy-and-safety-of-transarterial-therapies-using-ethiodized-oil-preclinical-review-in-liver-cancer-models
#10
Ron C Gaba, Regina M Schwind, Sebastien Ballet
PURPOSE: To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil-based locoregional therapy (LRT) for liver cancer in preclinical models. MATERIALS AND METHODS: A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil...
December 28, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/29276074/kinases-molecular-stage-directors-for-schistosome-development-and-differentiation
#11
REVIEW
Christoph G Grevelding, Simone Langner, Colette Dissous
Understanding schistosome biology is still a challenging mission. The reproductive biology of this parasitic trematode is closely associated with the pathologic consequences of schistosomiasis, the devastating infectious disease caused by members of the family Schistosomatidae worldwide. Recent studies of signaling mechanisms confirmed the prominent roles of protein kinases (PKs) in directing schistosome biology, and first evidence was obtained for an additional contribution of kinases with substrates different from proteins (non-PKs)...
December 21, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/29260614/neuroimaging-findings-in-pallister-killian-syndrome
#12
Emil Jernstedt Barkovich, Tarannum Musvee Lateef, Matthew T Whitehead
Pallister-Killian syndrome (PKS) is a rare chromosomal duplication disorder caused by additional copies of the short arm of chromosome 12 (12p). Clinically PKS is characterized by craniofacial dysmorphism with neonatal frontotemporal alopecia, hypertelorism, and low-set ears as well as kyphoscoliosis, severe intellectual disability, epilepsy, and abnormal muscle tone. Comprehensive high-resolution brain MR findings of PKS in childhood have not been previously illustrated in the medical literature. We present detailed neuroimaging findings from a child with PKS and thoroughly review previously reported structural brain abnormalities in this patient population...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/29247905/the-development-of-a-pregnancy-pbpk-model-for-bisphenol-a-and-its-evaluation-with-the-available-biomonitoring-data
#13
Raju Prasad Sharma, Marta Schuhmacher, Vikas Kumar
Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse birth outcomes. Estimation of the fetal plasma BPA concentration from the maternal plasma BPA would be highly useful to predict its associated risk to this specific population. The objective of current work is to develop a pregnancy-physiologically based pharmacokinetic (P-PBPK) model to predict the toxicokinetic profile of BPA in the fetus during gestational growth, and to evaluate the developed model using biomonitoring data obtained from different pregnancy cohort studies...
December 13, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29245037/production-of-bio-fertilizer-from-microwave-vacuum-pyrolysis-of-palm-kernel-shell-for-cultivation-of-oyster-mushroom-pleurotus-ostreatus
#14
Wai Lun Nam, Xue Yee Phang, Man Huan Su, Rock Keey Liew, Nyuk Ling Ma, Mohd Haqqi Nazilli Bin Rosli, Su Shiung Lam
Microwave vacuum pyrolysis of palm kernel shell (PKS) was performed to produce biochar, which was then tested as bio-fertilizer in growing Oyster mushroom (Pleurotus ostreatus). The pyrolysis approach produced biochar containing a highly porous structure with a high BET surface area of up to 270m2/g and low moisture content (≤10wt%), exhibiting desirable adsorption properties to be used as bio-fertilizer since it can act as a housing that provides many sites on which living microorganisms (mycelium or plant-growth promoting bacteria) and organic nutrients can be attached or adsorbed onto...
December 12, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29241934/fetoplacental-cytogenetic-discrepancy-in-a-pregnancy-with-fetal-mosaic-tetrasomy-12p-and-pallister-killian-syndrome-detected-by-amniocentesis
#15
Chih-Ping Chen, Liang-Kai Wang, Schu-Rern Chern, Peih-Shan Wu, Shin-Wen Chen, Shih-Ting Lai, Tzu-Yun Chuang, Li-Feng Chen, Wayseen Wang
OBJECTIVE: We present fetoplacental cytogenetic discrepancy in a pregnancy with prenatally detected mosaic tetrasomy 12p by amniocentesis. CASE REPORT: A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+i(12)(p10)[7]/46,XX[16]. Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from cultured amniocytes revealed arr (12p)×3, (X)×2...
December 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29236228/population-pharmacokinetic-pharmacodynamic-modeling-of-ropivacaine-in-spinal-anesthesia
#16
Zoubir Djerada, Catherine Feliu, Yoann Cazaubon, Faouzi Smati, Philippe Gomis, Dominique Guerrot, Beny Charbit, Olivier Fernandes, Jean-Marc Malinovsky
BACKGROUND: Ropivacaine is frequently used in spinal anesthesia but the relationship between plasma concentrations and sensory block level remains unknown. OBJECTIVE: The aim of this study was to assess the relationship between plasma ropivacaine concentrations and effects during spinal anesthesia. METHODS: Sixty patients aged between 18 and 82 years were included in this study after providing written informed consent. Patients were randomly assigned to receive intrathecal administration of ropivacaine 15, 20 or 25 mg...
December 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29228272/an-investigation-into-the-possible-regulation-of-the-expression-of-genes-by-yapa-in-talaromyces-marneffei-using-the-qrt-pcr-method
#17
Wiyada Dankai, Monsicha Pongpom, Nongnuch Vanittanakom
The pathogenic dimorphic fungus Talaromyces marneffei is known to cause a fatal systemic mycosis in immunocompromised patients, especially in HIV patients in Southeast Asia. The basic leucine-zipper (bZip) transcription factor gene, yapA, has been identified in T. marneffei. A prior study described that yapA was involved in the oxidative and nitrosative stress response in T. marneffei. Interestingly, an essential role of Saccharomyces cerevisiae Yap1p in the oxidative stress response is the activation of the transcription of its target genes...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29225701/cytotoxic-escherichia-coli-strains-encoding-colibactin-and-cytotoxic-necrotizing-factor-cnf-colonize-laboratory-macaques
#18
Yan Feng, Anthony Mannion, Carolyn M Madden, Alton G Swennes, Catherine Townes, Charles Byrd, Robert P Marini, James G Fox
Background: Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically-relevant infections. Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular differentiation, apoptosis and proliferation...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/29222831/a-review-of-structural-brain-abnormalities-in-pallister-killian-syndrome
#19
Cathryn Poulton, Gareth Baynam, Clarissa Yates, Hamid Alinejad-Rokny, Simon Williams, Helen Wright, Karen J Woodward, Soruba Sivamoorthy, Joanne Peverall, Peter Shipman, David Ravine, John Beilby, Julian Ik-Tsen Heng
BACKGROUND: Pallister-Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects. METHODS: We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS...
December 9, 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29216817/characterization-of-sulfhydryl-oxidase-from-aspergillus-tubingensis
#20
Outi Nivala, Greta Faccio, Mikko Arvas, Perttu Permi, Johanna Buchert, Kristiina Kruus, Maija-Liisa Mattinen
BACKGROUND: Despite of the presence of sulfhydryl oxidases (SOXs) in the secretomes of industrially relevant organisms and their many potential applications, only few of these enzymes have been biochemically characterized. In addition, basic functions of most of the SOX enzymes reported so far are not fully understood. In particular, the physiological role of secreted fungal SOXs is unclear. RESULTS: The recently identified SOX from Aspergillus tubingensis (AtSOX) was produced, purified and characterized in the present work...
December 8, 2017: BMC Biochemistry
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