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Metabolic engineering

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https://www.readbyqxmd.com/read/28098843/perm-hypothesis-the-fundamental-machinery-able-to-elucidate-the-role-of-xenobiotics-and-hormesis-in-cell-survival-and-homeostasis
#1
REVIEW
Salvatore Chirumbolo, Geir Bjørklund
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response...
January 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28096378/biosynthesis-of-the-microtubule-destabilizing-diterpene-pseudolaric-acid-b-from-golden-larch-involves-an-unusual-diterpene-synthase
#2
Sibongile Mafu, Prema Sambandaswami Karunanithi, Teresa Ann Palazzo, Bronwyn Lee Harrod, Selina Marakana Rodriguez, Iris Natalie Mollhoff, Terrence Edward O'Brien, Shen Tong, Oliver Fiehn, Dean J Tantillo, Jörg Bohlmann, Philipp Zerbe
The diversity of small molecules formed via plant diterpene metabolism offers a rich source of known and potentially new biopharmaceuticals. Among these, the microtubule-destabilizing activity of pseudolaric acid B (PAB) holds promise for new anticancer agents. PAB is found, perhaps uniquely, in the coniferous tree golden larch (Pseudolarix amabilis, Pxa). Here we describe the discovery and mechanistic analysis of golden larch terpene synthase 8 (PxaTPS8), an unusual diterpene synthase (diTPS) that catalyzes the first committed step in PAB biosynthesis...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095853/crispri-mediated-metabolic-engineering-of-e-coli-for-o-methylated-anthocyanin-production
#3
Brady F Cress, Quentin D Leitz, Daniel C Kim, Teresita D Amore, Jon Y Suzuki, Robert J Linhardt, Mattheos A G Koffas
BACKGROUND: Anthocyanins are a class of brightly colored, glycosylated flavonoid pigments that imbue their flower and fruit host tissues with hues of predominantly red, orange, purple, and blue. Although all anthocyanins exhibit pH-responsive photochemical changes, distinct structural decorations on the core anthocyanin skeleton also cause dramatic color shifts, in addition to improved stabilities and unique pharmacological properties. In this work, we report for the first time the extension of the reconstituted plant anthocyanin pathway from (+)-catechin to O-methylated anthocyanins in a microbial production system, an effort which requires simultaneous co-option of the endogenous metabolites UDP-glucose and S-adenosyl-L-methionine (SAM or AdoMet)...
January 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28094982/bacterial-genome-editing-via-a-designed-toxin-antitoxin-cassette
#4
Jie Wu, Aihua Deng, Qinyun Sun, Hua Bai, Zhaopeng Sun, Xiuling Shang, Yun Zhang, Qian Liu, Yong Liang, Shuwen Liu, Yongsheng Che, Tingyi Wen
Manipulating the bacterial genomes in an efficient manner is essential to biological and biotechnological research. Despite usage of various modules for genomic editing with counter-selectable markers including the toxin genes, an easy-to-use and highly designable toxin-antitoxin (TA) cassette without causing any leakages is urgently needed for efficient genome editing of the Gram-positive bacteria. Here, we reprogramed the bacterial TA systems as a toxin counter-selectable cassette regulated by an antitoxin switch (TCCRAS) for genetic modifications in the extensively studied and utilized Gram-positive bacteria, B...
January 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28094975/endoribonuclease-based-two-component-repressor-systems-for-tight-gene-expression-control-in-plants
#5
Yan Liang, Sarah M Richardson, Jingwei Yan, Veronica T Benites, Clarabelle Cheng-Yue, Thu Tran, Jenny Mortimer, Aindrila Mukhopadhyay, Jay D Keasling, Dominique Loque
Tight control and multifactorial regulation of gene expression are important challenges in genetic engineering and are critical for the development of regulatory circuits. Meeting these challenges will facilitate transgene expression regulation and support fine-tuning of metabolic pathways to avoid the accumulation of undesired intermediates. By employing the endoribonuclease Csy4 and its recognition sequence from Pseudomonas aeruginosa and manipulating 5'UTR of mRNA, we developed a two-component expression-repression system to tightly control synthesis of transgene products...
January 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28094080/respectful-modeling-addressing-uncertainty-in-dynamic-system-models-for-molecular-biology
#6
REVIEW
Areti Tsigkinopoulou, Syed Murtuza Baker, Rainer Breitling
Although there is still some skepticism in the biological community regarding the value and significance of quantitative computational modeling, important steps are continually being taken to enhance its accessibility and predictive power. We view these developments as essential components of an emerging 'respectful modeling' framework which has two key aims: (i) respecting the models themselves and facilitating the reproduction and update of modeling results by other scientists, and (ii) respecting the predictions of the models and rigorously quantifying the confidence associated with the modeling results...
January 13, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28093673/metagenomic-insights-into-effects-of-spent-engine-oil-perturbation-on-the-microbial-community-composition-and-function-in-a-tropical-agricultural-soil
#7
Lateef B Salam, Sunday O Obayori, Francisca O Nwaokorie, Aisha Suleiman, Raheemat Mustapha
Analyzing the microbial community structure and functions become imperative for ecological processes. To understand the impact of spent engine oil (SEO) contamination on microbial community structure of an agricultural soil, soil microcosms designated 1S (agricultural soil) and AB1 (agricultural soil polluted with SEO) were set up. Metagenomic DNA extracted from the soil microcosms and sequenced using Miseq Illumina sequencing were analyzed for their taxonomic and functional properties. Taxonomic profiling of the two microcosms by MG-RAST revealed the dominance of Actinobacteria (23...
January 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28092657/lipid-production-in-yarrowia-lipolytica-is-maximized-by-engineering-cytosolic-redox-metabolism
#8
Kangjian Qiao, Thomas M Wasylenko, Kang Zhou, Peng Xu, Gregory Stephanopoulos
Microbial factories have been engineered to produce lipids from carbohydrate feedstocks for production of biofuels and oleochemicals. However, even the best yields obtained to date are insufficient for commercial lipid production. To maximize the capture of electrons generated from substrate catabolism and thus increase substrate-to-product yields, we engineered 13 strains of Yarrowia lipolytica with synthetic pathways converting glycolytic NADH into the lipid biosynthetic precursors NADPH or acetyl-CoA. A quantitative model was established and identified the yield of the lipid pathway as a crucial determinant of overall process yield...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092361/designed-cell-consortia-as-fragrance-programmable-analog-to-digital-converters
#9
Marius Müller, Simon Ausländer, Andrea Spinnler, David Ausländer, Julian Sikorski, Marc Folcher, Martin Fussenegger
Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia...
January 16, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28092358/recurrent-rna-motifs-as-scaffolds-for-genetically-encodable-small-molecule-biosensors
#10
Ely B Porter, Jacob T Polaski, Makenna M Morck, Robert T Batey
Allosteric RNA devices are increasingly being viewed as important tools capable of monitoring enzyme evolution, optimizing engineered metabolic pathways, facilitating gene discovery and regulators of nucleic acid-based therapeutics. A key bottleneck in the development of these platforms is the availability of small-molecule-binding RNA aptamers that robustly function in the cellular environment. Although aptamers can be raised against nearly any desired target through in vitro selection, many cannot easily be integrated into devices or do not reliably function in a cellular context...
January 16, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28089747/metabolic-engineering-of-a-diazotrophic-bacterium-improves-ammonium-release-and-biofertilization-of-plants-and-microalgae
#11
Rafael Ambrosio, Juan Cesar Federico Ortiz-Marquez, Leonardo Curatti
The biological nitrogen fixation carried out by some Bacteria and Archaea is one of the most attractive alternatives to synthetic nitrogen fertilizers. However, with the exception of the symbiotic rhizobia-legumes system, progress towards a more extensive realization of this goal has been slow. In this study we manipulated the endogenous regulation of both nitrogen fixation and assimilation in the aerobic bacterium Azotobacter vinelandii. Substituting an exogenously inducible promoter for the native promoter of glutamine synthetase produced conditional lethal mutant strains unable to grow diazotrophically in the absence of the inducer...
January 9, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28089378/butyrate-production-under-aerobic-growth-conditions-by-engineered-escherichia-coli
#12
Naoya Kataoka, Alisa S Vangnai, Thunyarat Pongtharangkul, Toshiharu Yakushi, Kazunobu Matsushita
Butyrate is an important industrial platform chemical. Although several groups have reported butyrate production under oxygen-limited conditions by a native producer, Clostridium tyrobutylicum, and by a metabolically engineered Escherichia coli, efforts to produce butyrate under aerobic growth conditions have met limited success. Here, we constructed a novel butyrate synthetic pathway that functions under aerobic growth conditions in E. coli, by modifying the 1-butanol synthetic pathway reported previously...
January 11, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28089246/identification-and-characterization-of-l-lysine-decarboxylase-from-huperzia-serrata-and-its-role-in-the-metabolic-pathway-of-lycopodium-alkaloid
#13
Baofu Xu, Lei Lei, Xiaocen Zhu, Yiqing Zhou, Youli Xiao
Lysine decarboxylation is the first biosynthetic step of Huperzine A (HupA). Six cDNAs encoding lysine decarboxylases (LDCs) were cloned from Huperzia serrata by degenerate PCR and rapid amplification of cDNA ends (RACE). One HsLDC isoform was functionally characterized as lysine decarboxylase. The HsLDC exhibited greatest catalytic efficiency (kcat/Km, 2.11 s(-1) mM(-1)) toward L-lysine in vitro among all reported plant-LDCs. Moreover, transient expression of the HsLDC in tobacco leaves specifically increased cadaverine content from zero to 0...
January 12, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28088723/discovery-and-metagenomic-analysis-of-an-anammox-bacterial-enrichment-related-to-candidatus-brocadia-caroliniensis-in-a-full-scale-glycerol-fed-nitritation-denitritation-separate-centrate-treatment-process
#14
Hongkeun Park, Ariane C Brotto, Mark C M van Loosdrecht, Kartik Chandran
A distinctive red biofilm was observed in a glycerol-fed digester liquid effluent treatment process coupling partial nitrification (nitritation) and partial denitrification (denitritation) processes. Based on initial phylogenetic screening using 16S rRNA clone libraries and quantitative polymerase chain reaction, the biofilm was enriched in novel anaerobic ammonium oxidizing bacteria (AMX/anammox) closely related to Candidatus "Brocadia caroliniensis". The metabolic functionality of the C. "Brocadia caroliniensis" enrichment was further explored using high-throughput sequencing and de novo metagenome assembly...
January 6, 2017: Water Research
https://www.readbyqxmd.com/read/28088640/bioethanol-production-from-cellulosic-hydrolysates-by-engineered-industrial-saccharomyces-cerevisiae
#15
Ye-Gi Lee, Yong-Su Jin, Young-Lok Cha, Jin-Ho Seo
Even though industrial yeast strains exhibit numerous advantageous traits for the production of bioethanol, their genetic manipulation has been limited. This study demonstrates that an industrial polyploidy Saccharomyces cerevisiae JHS200 can be engineered through Cas9 (CRISPR associated protein 9)-based genome editing. Specifically, we generated auxotrophic mutants and introduced a xylose metabolic pathway into the auxotrophic mutants. As expected, the engineered strain (JX123) enhanced ethanol production from cellulosic hydrolysates as compared to other engineered haploid strains...
December 18, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/28088572/bcs-class-iv-drugs-highly-notorious-candidates-for-formulation-development
#16
REVIEW
Rohan Ghadi, Neha Dand
BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs...
January 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28088091/solar-to-chemical-and-solar-to-fuel-production-from-co2-by-metabolically-engineered-microorganisms
#17
REVIEW
Han Min Woo
Recent development of carbon capture utilization (CCU) for reduction of greenhouse gas emission are reviewed. In the case of CO2 utilization, I describe development of solar-to-chemical and solar-to-fuel technology that refers to the use of solar energy to convert CO2 to desired chemicals and fuels. Photoautotrophic cyanobacterial platforms have been extensively developed on this principle, producing a diverse range of alcohols, organic acids, and isoprenoids directly from CO2. Recent breakthroughs in the metabolic engineering of cyanobacteria were reviewed...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28087672/elimination-of-sucrose-transport-and-hydrolysis-in-saccharomyces-cerevisiae-a-platform-strain-for-engineering-sucrose-metabolism
#18
Wesley Leoricy Marques, Robert Mans, Eko Roy Marella, Rosa Lorizolla Cordeiro, Marcel van den Broek, Jean-Marc G Daran, Jack T Pronk, Andreas K Gombert, Antonius J A van Maris
Many relevant options to improve efficacy and kinetics of sucrose metabolism in Saccharomyces cerevisiae and, thereby, the economics of sucrose-based processes, remain to be investigated. An essential first step is to identify all native sucrose-hydrolysing enzymes and sucrose transporters in this yeast, including those that can be activated by suppressor mutations in sucrose-negative strains. A strain in which all known sucrose-transporter genes (MAL11, MAL21, MAL31, MPH2, MPH3) were deleted did not grow on sucrose after 2 months of incubation...
January 12, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28087530/pgas-a-low-ph-induced-promoter-as-a-dynamic-gene-expression-control-tool-for-the-metabolic-engineering-of-aspergillus-niger
#19
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
: The dynamic control of gene expression is important for adjusting fluxes in order to obtain desired products and achieve appropriate cell growth, particularly when the synthesis of a desired product drains metabolites required for cell growth. For dynamic gene expression, a promoter responsive to a particular environmental stressor is vital. Here, we report a low pH-inducible promoter, Pgas, which promotes minimal gene expression at pH values of greater than 5.0, but functioned efficiently at low pH values, such as pH 2...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28086783/de-novo-transcriptome-analysis-of-rose-scented-geranium-provides-insights-into-the-metabolic-specificity-of-terpene-and-tartaric-acid-biosynthesis
#20
Lokesh K Narnoliya, Girija Kaushal, Sudhir P Singh, Rajender S Sangwan
BACKGROUND: Rose-scented geranium (Pelargonium sp.) is a perennial herb that produces a high value essential oil of fragrant significance due to the characteristic compositional blend of rose-oxide and acyclic monoterpenoids in foliage. Recently, the plant has also been shown to produce tartaric acid in leaf tissues. Rose-scented geranium represents top-tier cash crop in terms of economic returns and significance of the plant and plant products. However, there has hardly been any study on its metabolism and functional genomics, nor any genomic expression dataset resource is available in public domain...
January 13, 2017: BMC Genomics
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