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https://www.readbyqxmd.com/read/28792770/proteomic-analysis-of-brain-and-cerebrospinal-fluid-from-the-three-major-forms-of-neuronal-ceroid-lipofuscinosis-reveals-potential-biomarkers
#1
David E Sleat, Abla Tannous, Istvan Sohar, Jennifer A Wiseman, Haiyan Zheng, Meiqian Qian, Caifeng Zhou, Winnie Xin, Rosemary Barone, Katherine B Sims, Dirk F Moore, Peter Lobel
Clinical trials have been conducted for the neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative lysosomal diseases that primarily affect children. While clinical rating systems will evaluate long-term efficacy, biomarkers to measure short-term response to treatment would be extremely valuable. To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease) and CLN3 protein (CLN3 disease)...
August 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28769963/tissue-specific-floral-transcriptome-analysis-of-the-sexually-deceptive-orchid-chiloglottis-trapeziformis-provides-insights-into-the-biosynthesis-and-regulation-of-its-unique-uv-b-dependent-floral-volatile-chiloglottone-1
#2
Darren C J Wong, Ranamalie Amarasinghe, Claudia Rodriguez-Delgado, Rodney Eyles, Eran Pichersky, Rod Peakall
The Australian sexually deceptive orchid, Chiloglottis trapeziformis, employs a unique UV-B-dependent floral volatile, chiloglottone 1, for specific male wasp pollinator attraction. Chiloglottone 1 and related variants (2,5-dialkylcyclohexane-1,3-diones), represent a unique class of specialized metabolites presumed to be the product of cyclization between two fatty acid (FA) precursors. However, the genes involved in the biosynthesis of precursors, intermediates, and transcriptional regulation remains to be discovered...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28741300/the-hotdog-fold-thioesterase-pa1618-catalytic-mechanism-revealed-by-x-ray-structure-determination-of-the-substrate-oxygen-ester-analog-complex
#3
John A Latham, Tianyang Ji, Kaila Matthews, Patrick Mariano, Karen N Allen, Debra Dunaway-Mariano
Thioesterase activity (hydrolysis of thioester bonds) accounts for the majority of the activities in the hotdog-fold superfamily. The structure and mechanism of catalysis for many hotdog enzymes have been elucidated by X-ray crystallography and kinetics to probe the specific substrate usage and cellular functions. However, structures of hotdog thioesterases in complex with substrate analogs reported to date utilize ligands that comprise either truncations of the substrate or include additional atoms to prevent the hydrolysis...
July 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28684428/a-lipid-anchored-nac-transcription-factor-is-translocated-into-the-nucleus-and-activates-glyoxalase-i-expression-during-drought-stress
#4
Mei Duan, Rongxue Zhang, Fugui Zhu, Zhenqian Zhang, Lanming Gou, Jiangqi Wen, Jiangli Dong, Tao Wang
The plant-specific NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play a vital role in the response to drought stress. Here, we report a lipid-anchored NACsa TF in Medicago falcata MfNACsa is an essential regulator of plant tolerance to drought stress, resulting in the differential expression of genes involved in oxidation reduction and lipid transport and localization. MfNACsa is associated with membranes under unstressed conditions and, more specifically, is targeted to the plasma membrane through S-palmitoylation...
July 2017: Plant Cell
https://www.readbyqxmd.com/read/28673981/synergistic-effects-of-treating-the-spinal-cord-and-brain-in-cln1-disease
#5
Charles Shyng, Hemanth R Nelvagal, Joshua T Dearborn, Jaana Tyynelä, Robert E Schmidt, Mark S Sands, Jonathan D Cooper
Infantile neuronal ceroid lipofuscinosis (INCL, or CLN1 disease) is an inherited neurodegenerative storage disorder caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). It was widely believed that the pathology associated with INCL was limited to the brain, but we have now found unexpectedly profound pathology in the human INCL spinal cord. Similar pathological changes also occur at every level of the spinal cord of PPT1-deficient (Ppt1(-/-) ) mice before the onset of neuropathology in the brain...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28669536/development-of-a-novel-lead-that-targets-m-%C3%A2-tuberculosis-polyketide-synthase-13
#6
Anup Aggarwal, Maloy K Parai, Nishant Shetty, Deeann Wallis, Lisa Woolhiser, Courtney Hastings, Noton K Dutta, Stacy Galaviz, Ramesh C Dhakal, Rupesh Shrestha, Shoko Wakabayashi, Chris Walpole, David Matthews, David Floyd, Paul Scullion, Jennifer Riley, Ola Epemolu, Suzanne Norval, Thomas Snavely, Gregory T Robertson, Eric J Rubin, Thomas R Ioerger, Frik A Sirgel, Ruben van der Merwe, Paul D van Helden, Peter Keller, Erik C Böttger, Petros C Karakousis, Anne J Lenaerts, James C Sacchettini
Widespread resistance to first-line TB drugs is a major problem that will likely only be resolved through the development of new drugs with novel mechanisms of action. We have used structure-guided methods to develop a lead molecule that targets the thioesterase activity of polyketide synthase Pks13, an essential enzyme that forms mycolic acids, required for the cell wall of Mycobacterium tuberculosis. Our lead, TAM16, is a benzofuran class inhibitor of Pks13 with highly potent in vitro bactericidal activity against drug-susceptible and drug-resistant clinical isolates of M...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28644971/simultaneous-silencing-of-ghfad2-1-and-ghfatb-enhances-the-quality-of-cottonseed-oil-with-high-oleic-acid
#7
Feng Liu, Yan-Peng Zhao, Hua-Guo Zhu, Qian-Hao Zhu, Jie Sun
Cottonseed oil has become an important source of edible oil due to its significant cost advantage. However, there is a growing concern over its fatty acid composition and nutritional value. In Gossypium hirsutum, GhFAD2-1 and GhFATB encoding the microsomal oleate desaturase and palmitoyl-acyl carrier protein thioesterase, respectively, play critical roles in regulating the proportions of saturated and polyunsaturated fatty acids in cottonseed lipids. In this study, RNAi technology was used to simultaneously inhibit the expression levels of GhFAD2-1 and GhFATB to improve the quality of cottonseed oil by increasing oleic acid content...
June 15, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28638070/thioesterase-ybgc-affects-motility-by-modulating-c-di-gmp-levels-in-shewanella-oneidensis
#8
Tong Gao, Qiu Meng, Haichun Gao
Because of ubiquity of thioesters, thioesterases play a critical role in metabolism, membrane biosynthesis, signal transduction, and gene regulation. In many bacteria, YbgC is such an enzyme, whose coding gene mostly resides in the tol-pal cluster. Although all other proteins encoded in the tol-pal cluster are clearly involved in maintaining cell envelope integrity and cell division, little is known about the physiological role of YbgC. In this study, we identify in Shewanella oneidensis, a γ-proteobacterium used as a research model for environmental microbes, YbgC as a motility regulator...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#9
Nicholas C Harris, Michio Sato, Nicolaus A Herman, Frederick Twigg, Wenlong Cai, Joyce Liu, Xuejun Zhu, Jordan Downey, Ryan Khalaf, Joelle Martin, Hiroyuki Koshino, Wenjun Zhang
A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28607105/acyl-coa-thioesterase-1-acot1-regulates-ppar%C3%AE-to-couple-fatty-acid-flux-with-oxidative-capacity-during-fasting
#10
Mallory P Franklin, Aishwarya Sathyanarayan, Douglas G Mashek
Hepatic acyl-CoA thioesterase 1 (ACOT1) catalyzes the conversion of acyl-CoAs to fatty acids (FAs) and CoA. We sought to determine the role of ACOT1 in hepatic lipid metabolism in C57Bl/6J male mice 1 week after adenovirus-mediated Acot1 knockdown. Acot1 knockdown reduced liver triglyceride (TG) as a result of enhanced TG hydrolysis and subsequent FA oxidation. In vitro experiments demonstrated that Acot1 knockdown led to greater TG turnover and FA oxidation, suggesting that ACOT1 is important for controlling the rate of FA oxidation...
August 2017: Diabetes
https://www.readbyqxmd.com/read/28599448/overexpression-of-the-androgen-receptor-in-human-hepatoma-cells-and-its-effect-on-fatty-acid-metabolism
#11
Tatsuo Kanda, Xia Jiang, Masato Nakamura, Yuki Haga, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Fumio Imazeki, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28587908/elevating-4-hydroxycoumarin-production-through-alleviating-thioesterase-mediated-salicoyl-coa-degradation
#12
Xiaolin Shen, Monika Mahajani, Jia Wang, Yaping Yang, Qipeng Yuan, Yajun Yan, Yuheng Lin
Acyl-CoAs are essential intermediates in the biosynthetic pathways of a number of industrially and pharmaceutically important molecules. When these pathways are reconstituted in a heterologous microbial host for metabolic engineering purposes, the acyl-CoAs may be subject to undesirable hydrolysis by the host's native thioesterases, resulting in a waste of cellular energy and decreased intermediate availability, thus impairing bioconversion efficiency. 4-hydroxycoumarin (4HC) is a direct synthetic precursor to the commonly used oral anticoagulants (e...
July 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28558229/catalytic-dyad-in-the-sgnh-hydrolase-superfamily-in-depth-insight-into-structural-parameters-tuning-the-catalytic-process-of-extracellular-lipase-from-streptomyces-rimosus
#13
Ivana Leščić Ašler, Zoran Štefanić, Aleksandra Maršavelski, Robert Vianello, Biserka Kojić-Prodić
SrLip is an extracellular enzyme from Streptomyces rimosus (Q93MW7) exhibiting lipase, phospholipase, esterase, thioesterase, and tweenase activities. The structure of SrLip is one of a very few lipases, among the 3D-structures of the SGNH superfamily of hydrolases, structurally characterized by synchrotron diffraction data at 1.75 Å resolution (PDB: 5MAL ). Its crystal structure was determined by molecular replacement using a homology model based on the crystal structure of phospholipase A1 from Streptomyces albidoflavus (PDB: 4HYQ )...
June 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28550989/biosynthesis-of-medium-chain-length-alkanes-for-bio-aviation-fuel-by-metabolic-engineered-escherichia-coli
#14
Meng Wang, Kaili Nie, Hao Cao, Haijun Xu, Yunming Fang, Tianwei Tan, Jan Baeyens, Luo Liu
The aim of this work was to study the synthesis of medium-chain length alkanes (MCLA), as bio-aviation product. To control the chain length of alkanes and increase the production of MCLA, Escherichia coli cells were engineered by incorporating (i) a chain length specific thioesterase from Umbellularia californica (UC), (ii) a plant origin acyl carrier protein (ACP) gene and (iii) the whole fatty acid synthesis system (FASs) from Jatropha curcas (JC). The genetic combination was designed to control the product spectrum towards optimum MCLA...
September 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28522606/structural-analysis-of-the-dual-function-thioesterase-sav606-unravels-the-mechanism-of-michael-addition-of-glycine-to-an-%C3%AE-%C3%AE-unsaturated-thioester
#15
Taichi Chisuga, Akimasa Miyanaga, Fumitaka Kudo, Tadashi Eguchi
Thioesterases catalyze hydrolysis of acyl thioesters to release carboxylic acid or macrocyclization to produce the corresponding macrocycle in the biosynthesis of fatty acids, polyketides, or nonribosomal peptides. Recently, we reported that the thioesterase CmiS1 from Streptomyces sp. MJ635-86F5 catalyzes the Michael addition of glycine to an α,β-unsaturated fatty acyl thioester followed by thioester hydrolysis in the biosynthesis of the macrolactam antibiotic cremimycin. However, the molecular mechanisms of CmiS1-catalyzed reactions are unclear...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28518146/acyl-coa-thioesterase-7-is-involved-in-cell-cycle-progression-via-regulation-of-pkc%C3%AE-p53-p21-signaling-pathway
#16
Seung Hee Jung, Hyung Chul Lee, Hyun Jung Hwang, Hyun A Park, Young-Ah Moon, Bong Cho Kim, Hyeong Min Lee, Kwang Pyo Kim, Yong-Nyun Kim, Byung Lan Lee, Jae Cheol Lee, Young-Gyu Ko, Heon Joo Park, Jae-Seon Lee
Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53-p21 signaling pathway without a DNA damage response...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28504677/%C3%AE-lactone-formation-during-product-release-from-a-nonribosomal-peptide-synthetase
#17
Jason E Schaffer, Margaret R Reck, Neha K Prasad, Timothy A Wencewicz
Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic assembly lines that polymerize amino acids into a myriad of biologically active nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse release strategies for off-loading thioester-tethered polymeric peptides from termination modules typically via hydrolysis, aminolysis, or cyclization to provide mature antibiotics as carboxylic acids/esters, amides, and lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28475114/melatonin-and-vitamin-d-interfere-with-the-adipogenic-fate-of-adipose-derived-stem-cells
#18
Valentina Basoli, Sara Santaniello, Sara Cruciani, Giorgio Carlo Ginesu, Maria Laura Cossu, Alessandro Palmerio Delitala, Pier Andrea Serra, Carlo Ventura, Margherita Maioli
Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28465060/biosynthesis-of-the-fatty-acid-isopropyl-esters-by-engineered-escherichia-coli
#19
Hong Pan, Lihua Zhang, Xun Li, Daoyi Guo
The fatty acid methyl esters and fatty acid ethyl esters are known as biodiesels which are considered to be renewable, nontoxic and biodegradable biofuels. However, the conventional biodiesels show a high crystallization temperature which is one of the most critical obstacles against the widespread biodiesel usage. The high crystallization temperature of biodiesel can be reduced by replacing the methyl or ethyl ester with an isopropyl moiety. Here we report on a strategy to establish biosynthesis of the fatty acid isopropyl esters(FAIPEs) from the simple substrate glucose in Escherichia coli with heterologous coexpression of atoB encoded acetyl-CoA acetyltransferase and atoAD encode acetoacetyl-CoA transferase from E...
July 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28454735/biosynthesis-inspired-deracemizative-production-of-d-luciferin-by-combining-luciferase-and-thioesterase
#20
Juri Maeda, Dai-Ichiro Kato, Masatoshi Okuda, Masahiro Takeo, Seiji Negoro, Kazunari Arima, Yuji Ito, Kazuki Niwa
Due to the strict enantioselectivity of firefly luciferase, only d-luciferin can be used as a substrate for bioluminescence reactions. Unfortunately, luciferin racemizes easily and accumulation of nonluminous l-luciferin has negative influences on the light emitting reaction. Thus, maintaining the enantiopurity of luciferin in the reaction mixture is one of the most important demands in bioluminescence applications using firefly luciferase. In fireflies, however, l-luciferin is the biosynthetic precursor of d-luciferin, which is produced from the L-form undergoing deracemization...
August 2017: Biochimica et Biophysica Acta
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