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https://www.readbyqxmd.com/read/27920298/malate-synthase-and-%C3%AE-methylmalyl-coa-lyase-reactions-in-the-methylaspartate-cycle-in-haloarcula-hispanica
#1
Farshad Borjian, Jing Han, Jing Hou, Hua Xiang, Jan Zarzycki, Ivan A Berg
: Haloarchaea are extremely halophilic heterotrophic microorganisms belonging to the class Halobacteria (Euryarchaeota). Almost half of the haloarchaea possesses the genes coding for enzymes of the methylaspartate cycle, a recently discovered anaplerotic acetate assimilation pathway. In this cycle, the enzymes of the tricarboxylic acid cycle together with the dedicated enzymes of the methylaspartate cycle convert two acetyl-CoA molecules to malate. The methylaspartate cycle involves two reactions catalyzed by homologous enzymes belonging to the CitE-like enzyme superfamily, the malyl-CoA lyase/thioesterase (haloarchaeal malate synthase, hMS, Hah_2476 in Haloarcula hispanica) and the β-methylmalyl-CoA lyase (hMCL, Hah_1341)...
December 5, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27897367/bifunctionality-of-activ-as-a-cyclase-thioesterase-revealed-by-in-vitro-reconstitution-of-actinorhodin-biosynthesis-in-streptomyces-coelicolor-a3-2
#2
Takaaki Taguchi, Takayoshi Awakawa, Yukitaka Nishihara, Michiho Kawamura, Yasuo Ohnishi, Koji Ichinose
Type II polyketide synthase (PKS) iteratively generates a nascent polyketide thioester of acyl carrier protein (ACP), which is structurally modified to produce an ACP-free intermediate towards its final metabolite. However, the timing of ACP off-loading is not well defined due to the lack of an apparent thioesterase (TE) among relevant biosynthetic enzymes. Here, ActIV, which had been assigned as a second ring cyclase (CYC) in actinorhodin (ACT) biosynthesis, was shown to possess a TE activity in vitro with a model substrate, anthraquinone-2-carboxylic acid-N-acetylcysteamine...
November 29, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27845206/both-a-pks-and-a-pptase-are-involved-in-melanin-biosynthesis-and-regulation-of-aureobasidium-melanogenum-xj5-1-isolated-from-the-taklimakan-desert
#3
Hong Jiang, Guang-Lei Liu, Zhe Chi, Jian-Ming Wang, Ly-Ly Zhang, Zhen-Ming Chi
A PKS1 gene responsible for the melanin biosynthesis and a NPG1 gene in Aureobasidium melanogenum XJ5-1 were cloned and characterized. An ORF of the PKS1 gene encoding a protein with 2165 amino acids contained 6495bp while an ORF of the NPG1 gene encoding a protein with 340 amino acids had 1076bp. After analysis of their promoters, it was found that expression of both the PKS1 gene and the NPG1 gene was repressed by nitrogen sources and glucose, respectively. The PKS deduced from the cloned gene consisted of one ketosynthase, one acyl transferase, two acyl carrier proteins, one thioesterase and one cyclase while the PPTase belonged to the family Sfp-type...
November 11, 2016: Gene
https://www.readbyqxmd.com/read/27765741/mri-brain-volume-measurements-in-infantile-neuronal-ceroid-lipofuscinosis
#4
E H Baker, S W Levin, Z Zhang, A B Mukherjee
BACKGROUND AND PURPOSE: Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase 1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood death. As part of a project studying the treatment benefits of a combination of cysteamine bitartrate and N-acetyl cysteine, we made serial measurements of patients' brain volumes with MR imaging...
October 20, 2016: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/27761152/improvement-of-free-fatty-acid-production-using-a-mutant-acyl-coa-thioesterase-i-with-high-specific-activity-in-escherichia-coli
#5
Kwang Soo Shin, Sangwoo Kim, Sung Kuk Lee
BACKGROUND: Microbial production of oleochemicals has been actively studied in the last decade. Free fatty acids (FFAs) could be converted into a variety of molecules such as industrial products, consumer products, and fuels. FFAs have been produced in metabolically engineered Escherichia coli cells expressing a signal sequence-deficient acyl-CoA thioesterase I ('TesA). Nonetheless, increasing the expression level of 'TesA seems not to be an appropriate approach to scale up FFA production because a certain ratio of each component including fatty acid synthase and 'TesA is required for optimal production of FFAs...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/27748579/molecular-mechanism-for-isoform-selective-inhibition-of-acyl-protein-thioesterases-1-and-2-apt1-and-apt2
#6
Sang Joon Won, Dahvid Davda, Kristin J Labby, Sin Ye Hwang, Rachel Pricer, Jaimeen D Majmudar, Kira A Armacost, Laura A Rodriguez, Christina L Rodriguez, Fei San Chong, Kristopher A Torossian, Jasmine Palakurthi, Edward S Hur, Jennifer L Meagher, Charles L Brooks, Jeanne A Stuckey, Brent R Martin
Post-translational S-palmitoylation directs the trafficking and membrane localization of hundreds of cellular proteins, often involving a coordinated palmitoylation cycle that requires both protein acyl transferases (PATs) and acyl protein thioesterases (APTs) to actively redistribute S-palmitoylated proteins toward different cellular membrane compartments. This process is necessary for the trafficking and oncogenic signaling of S-palmitoylated Ras isoforms, and potentially many peripheral membrane proteins...
October 31, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27738839/functional-genomics-analysis-of-free-fatty-acid-production-under-continuous-phosphate-limiting-conditions
#7
J Tyler Youngquist, Travis C Korosh, Brian F Pfleger
Free fatty acids (FFA) are an attractive platform chemical that serves as a functional intermediate in metabolic pathways for producing oleochemicals. Many groups have established strains of Escherichia coli capable of producing various chain-length mixtures of FFA by heterologous expression of acyl-ACP thioesterases. For example, high levels of dodecanoic acid are produced by an E. coli strain expressing the Umbellularia californica FatB2 thioesterase, BTE. Prior studies achieved high dodecanoic acid yields and productivities under phosphate-limiting media conditions...
October 13, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27734184/biosynthesis-regulation-and-engineering-of-a-linear-polyketide-tautomycetin-a-novel-immunosuppressant-in-streptomyces-sp-ck4412
#8
Si-Sun Choi, Hee-Ju Nah, Hye-Rim Pyeon, Eung-Soo Kim
Tautomycetin (TMC) is a natural product with a linear structure that includes an ester bond connecting a dialkylmaleic moiety to a type I polyketide chain. Although TMC was originally identified as an antifungal antibiotic in the late 1980s, follow-up studies revealed its novel immunosuppressant activity. Specifically, TMC exhibited a mechanistically unique immunosuppressant activity about 100 times higher than that of cyclosporine A, a widely used immunosuppressant drug. Interestingly, a structurally close relative, tautomycin (TTM), was reported to not possess TMC-like immunosuppressant activity, suggesting that a distinctive polyketide moiety of TMC plays a critical role in immunosuppressant activity...
October 12, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27722792/decreased-sensitivity-of-palmitoyl-protein-thioesterase-1-deficient-neurons-to-chemical-anoxia
#9
Meredith Meyer, Attila D Kovács, David A Pearce
Infantile CLN1 disease, also known as infantile neuronal ceroid lipofuscinosis, is a fatal childhood neurodegenerative disorder caused by mutations in the CLN1 gene. CLN1 encodes a soluble lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1), and it is still unclear why neurons are selectively vulnerable to the loss of PPT1 enzyme activity in infantile CLN1 disease. To examine the effects of PPT1 deficiency on several well-defined neuronal signaling and cell death pathways, different toxic insults were applied in cerebellar granule neuron cultures prepared from wild type (WT) and palmitoyl protein thioesterase 1-deficient (Ppt1 (-/-) ) mice, a model of infantile CLN1 disease...
October 8, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27681913/new-dimensions-in-microbial-ecology-functional-genes-in-studies-to-unravel-the-biodiversity-and-role-of-functional-microbial-groups-in-the-environment
#10
REVIEW
Johannes F Imhoff
During the past decades, tremendous advances have been made in the possibilities to study the diversity of microbial communities in the environment. The development of methods to study these communities on the basis of 16S rRNA gene sequences analysis was a first step into the molecular analysis of environmental communities and the study of biodiversity in natural habitats. A new dimension in this field was reached with the introduction of functional genes of ecological importance and the establishment of genetic tools to study the diversity of functional microbial groups and their responses to environmental factors...
May 24, 2016: Microorganisms
https://www.readbyqxmd.com/read/27681620/structure-guided-enzymology-of-the-lipid-a-acyltransferase-lpxm-reveals-a-dual-activity-mechanism
#11
Dustin Dovala, Christopher M Rath, Qijun Hu, William S Sawyer, Steven Shia, Robert A Elling, Mark S Knapp, Louis E Metzger
Gram-negative bacteria possess a characteristic outer membrane, of which the lipid A constituent elicits a strong host immune response through the Toll-like receptor 4 complex, and acts as a component of the permeability barrier to prevent uptake of bactericidal compounds. Lipid A species comprise the bulk of the outer leaflet of the outer membrane and are produced through a multistep biosynthetic pathway conserved in most Gram-negative bacteria. The final steps in this pathway involve the secondary acylation of lipid A precursors...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27667141/discovery-of-a-mosaic-like-biosynthetic-assembly-line-with-a-decarboxylative-off-loading-mechanism-through-a-combination-of-genome-mining-and-imaging
#12
Mahsa Mir Mohseni, Thomas Höver, Lena Barra, Marcel Kaiser, Pieter C Dorrestein, Jeroen S Dickschat, Till F Schäberle
The biosynthetic gene cluster for the antiplasmodial natural product siphonazole was identified by using a combination of genome mining, imaging, and expression studies in the natural producer Herpetosiphon sp. B060. The siphonazole backbone is assembled from an unusual starter unit from the shikimate pathway that is extended by the action of polyketide synthases and non-ribosomal peptide synthetases with unusual domain structures, including several split modules and a large number of duplicated domains and domains predicted to be inactive...
October 17, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27597544/structures-of-a-nonribosomal-peptide-synthetase-module-bound-to-mbth-like-proteins-support-a-highly-dynamic-domain-architecture
#13
Bradley R Miller, Eric J Drake, Ce Shi, Courtney C Aldrich, Andrew M Gulick
Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27588038/structure-oriented-substrate-specificity-engineering-of-aldehyde-deformylating-oxygenase-towards-aldehydes-carbon-chain-length
#14
Luyao Bao, Jian-Jun Li, Chenjun Jia, Mei Li, Xuefeng Lu
BACKGROUND: Aldehyde-deformylating oxygenase (ADO) is an important enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, ADO exhibits quite low chain-length specificity with respect to the substrates ranging from C4 to C18 aldehydes, which is not suitable for producing fuels with different properties or different chain lengths. RESULTS: Based on the crystal structures of cADOs (cyanobacterial ADO) with substrate analogs bound, some amino acids affecting the substrate specificity of cADO were identified, including the amino acids close to the aldehyde group and the hydrophobic tail of the substrate and those along the substrate channel...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/27559295/in-silico-structure-prediction-of-human-fatty-acid-synthase-dehydratase-a-plausible-model-for-understanding-active-site-interactions
#15
Arun John, Vetrivel Umashankar, A Samdani, Manoharan Sangeetha, Subramanian Krishnakumar, Perinkulam Ravi Deepa
Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported...
2016: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/27553878/diagnosis-of-neuronal-ceroid-lipofuscinosis-type-2-cln2-disease-expert-recommendations-for-early-detection-and-laboratory-diagnosis
#16
Michael Fietz, Moeenaldeen AlSayed, Derek Burke, Jessica Cohen-Pfeffer, Jonathan D Cooper, Lenka Dvořáková, Roberto Giugliani, Emanuela Izzo, Helena Jahnová, Zoltan Lukacs, Sara E Mole, Ines Noher de Halac, David A Pearce, Helena Poupetova, Angela Schulz, Nicola Specchio, Winnie Xin, Nicole Miller
Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2-4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death...
September 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27520812/synthesis-gas-syngas-derived-medium-chain-length-polyhydroxyalkanoate-synthesis-in-engineered-rhodospirillum-rubrum
#17
Daniel Heinrich, Matthias Raberg, Philipp Fricke, Shane T Kenny, Laura Morales-Gamez, Ramesh P Babu, Kevin E O'Connor, Alexander Steinbüchel
: The purple nonsulfur alphaproteobacterium Rhodospirillum rubrum S1 was genetically engineered to synthesize a heteropolymer of mainly 3-hydroxydecanoic acid and 3-hydroxyoctanoic acid [P(3HD-co-3HO)] from CO- and CO2-containing artificial synthesis gas (syngas). For this, genes from Pseudomonas putida KT2440 coding for a 3-hydroxyacyl acyl carrier protein (ACP) thioesterase (phaG), a medium-chain-length (MCL) fatty acid coenzyme A (CoA) ligase (PP_0763), and an MCL polyhydroxyalkanoate (PHA) synthase (phaC1) were cloned and expressed under the control of the CO-inducible promoter PcooF from R...
October 15, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27497785/identification-of-interacting-proteins-with-aryl-hydrocarbon-receptor-in-scallop-chlamys-farreri-by-yeast-two-hybrid-screening
#18
Yuefeng Cai, Luqing Pan, Jingjing Miao, Tong Liu
The aryl hydrocarbon receptor (AhR) belongs to the basic-helix-loop helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors. AhR has been known primarily for its role in the regulation of several drug and xenobiotic metabolizing enzymes, as well as the mediation of the toxicity of certain xenobiotics, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Although the AhR is well-studied as a mediator of the toxicity of certain xenobiotics in marine bivalves, the normal physiological function remains unknown...
November 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27494047/engineering-of-new-pneumocandin-side-chain-analogues-from-glarea-lozoyensis-by-mutasynthesis-and-evaluation-of-their-antifungal-activity
#19
Li Chen, Yan Li, Qun Yue, Anna Loksztejn, Kenichi Yokoyama, Edd A Felix, Xingzhong Liu, Ningyan Zhang, Zhiqiang An, Gerald F Bills
Pneumocandins are lipohexapeptides of the echinocandin family that inhibit fungal 1,3-β-glucan synthase. Most of the pathway steps have been identified previously. However, the lipoinitiation reaction has not yet been experimentally verified. Herein, we investigate the lipoinitiation step of pneumocandin biosynthesis in Glarea lozoyensis and demonstrate that the gene product, GLligase, catalyzes this step. Disruption of GLHYD, a gene encoding a putative type II thioesterase and sitting upstream of the pneumocandin acyl side chain synthase gene, GLPKS4, revealed that GLHYD was necessary for optimal function of GLPKS4 and to attain normal levels of pneumocandin production...
October 21, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27466817/engineered-production-of-short-chain-fatty-acid-in-escherichia-coli-using-fatty-acid-synthesis-pathway
#20
Kamran Jawed, Anu Jose Mattam, Zia Fatma, Saima Wajid, Malik Z Abdin, Syed Shams Yazdani
Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity...
2016: PloS One
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