journal
MENU ▼
Read by QxMD icon Read
search

Metabolic Engineering

journal
https://www.readbyqxmd.com/read/28323063/lipid-engineering-reveals-regulatory-roles-for-membrane-fluidity-in-yeast-flocculation-and-oxygen-limited-growth
#1
Daniel Degreif, Tristan de Rond, Adam Bertl, Jay D Keasling, Itay Budin
Cells modulate lipid metabolism in order to maintain membrane homeostasis. Here we use a metabolic engineering approach to manipulate the stoichiometry of fatty acid unsaturation, a regulator of cell membrane fluidity, in Saccharomyces cerevisiae. Unexpectedly, reduced lipid unsaturation triggered cell-cell adhesion (flocculation), a phenomenon characteristic of industrial yeast but uncommon in laboratory strains. We find that ER lipid saturation sensors induce expression of FLO1 - encoding a cell wall polysaccharide binding protein - independently of its canonical regulator...
March 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28286292/metabolic-engineering-of-escherichia-coli-for-the-production-of-2-fucosyllactose-and-3-fucosyllactose-through-modular-pathway-enhancement
#2
Di Huang, Kexin Yang, Jia Liu, Yingying Xu, Yuanyuan Wang, Ru Wang, Bin Liu, Lu Feng
Fucosyllactoses, including 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), are important oligosaccharides in human milk that are commonly used as nutritional additives in infant formula due to their biological functions, such as the promotion of bifidobacteria growth, inhibition of pathogen infection, and improvement of immune response. In this study, we developed a synthetic biology approach to promote the efficient biosynthesis of 2'-FL and 3-FL in engineered Escherichia coli. To boost the production of 2'-FL and 3-FL, multiple modular optimization strategies were applied in a plug-and-play manner...
March 9, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28238759/in-vitro-metabolic-engineering-for-the-production-of-%C3%AE-ketoglutarate
#3
Barbara Beer, André Pick, Volker Sieber
α-Ketoglutarate (aKG) represents a central intermediate of cell metabolism. It is used for medical treatments and as a chemical building block. Enzymatic cascade reactions have the potential to sustainably synthesize this natural product. Here we report a systems biocatalysis approach for an in vitro reaction set-up to produce aKG from glucuronate using the oxidative pathway of uronic acids. Because of two dehydrations, a decarboxylation, and reaction conditions favoring oxidation, the pathway is driven thermodynamically towards complete product formation...
February 22, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28232136/metabolic-anchor-reactions-for-robust-biorefining
#4
Paula Jouhten, Jaime Huerta-Cepas, Peer Bork, Kiran Raosaheb Patil
Microbial cell factories based on renewable carbon sources are fundamental to a sustainable bio-economy. The economic feasibility of producer cells requires robust performance balancing growth and production. However, the inherent competition between these two objectives often leads to instability and reduces productivity. While algorithms exist to design metabolic network reduction strategies for aligning these objectives, the biochemical basis of the growth-product coupling has remained unresolved. Here, we reveal key reactions in the cellular biochemical repertoire as universal anchor reactions for aligning cell growth and production...
February 21, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28232235/estimation-of-flux-ratios-without-uptake-or-release-data-application-to-serine-and-methionine-metabolism
#5
Roland Nilsson, Irena Roci, Jeramie Watrous, Mohit Jain
Model-based metabolic flux analysis (MFA) using isotope-labeled substrates has provided great insight into intracellular metabolic activities across a host of organisms. One challenge with applying MFA in mammalian systems, however, is the need for absolute quantification of nutrient uptake, biomass composition, and byproduct release fluxes. Such measurements are often not feasible in complex culture systems or in vivo. One way to address this issue is to estimate flux ratios, the fractional contribution of a flux to a metabolite pool, which are independent of absolute measurements and yet informative for cellular metabolism...
February 20, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28216105/increasing-the-carbohydrate-storage-capacity-of-plants-by-engineering-a-glycogen-like-polymer-pool-in-the-cytosol
#6
Simona Eicke, David Seung, Barbara Egli, Emanuel A Devers, Sebastian Streb
Global demand for higher crop yields and for more efficient utilization of agricultural products will grow over the next decades. Here, we present a new concept for boosting the carbohydrate content of plants, by channeling photosynthetically fixed carbon into a newly engineered glucose polymer pool. We transiently expressed the starch/glycogen synthases from either Saccharomyces cerevisiae or Cyanidioschyzon merolae, together with the starch branching enzyme from C. merolae, in the cytosol of Nicotiana benthamiana leaves...
February 17, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28216108/crispr-enabled-trackable-genome-engineering-for-isopropanol-production-in-escherichia-coli
#7
Liya Liang, Rongming Liu, Andrew D Garst, Thomas Lee, Violeta Sànchez I Nogué, Gregg T Beckham, Ryan T Gill
Isopropanol is an important target molecule for sustainable production of fuels and chemicals. Increases in DNA synthesis and synthetic biology capabilities have resulted in the development of a range of new strategies for the more rapid design, construction, and testing of production strains. Here, we report on the use of such capabilities to construct and test 903 different variants of the isopropanol production pathway in Escherichia coli. We first constructed variants to explore the effect of codon optimization, copy number, and translation initiation rates on isopropanol production...
February 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28216107/an-endoplasmic-reticulum-engineered-yeast-platform-for-overproduction-of-triterpenoids
#8
Philipp Arendt, Karel Miettinen, Jacob Pollier, Riet De Rycke, Nico Callewaert, Alain Goossens
Saponins are a structurally diverse family of triterpenes that are widely found as main constituents in many traditional plant-based medicines and often have bioactivities of industrial interest. The heterologous production of triterpene saponins in microbes remains challenging and only limited successful pathway engineering endeavors have been reported. To improve the production capacities of a Saccharomyces cerevisiae saponin production platform, we assessed the effects of several hitherto unexplored gene knockout targets on the heterologous production of triterpenoids...
February 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28216106/metabolic-engineering-of-a-haploid-strain-derived-from-a-triploid-industrial-yeast-for-producing-cellulosic-ethanol
#9
Soo Rin Kim, Jeffrey M Skerker, In Iok Kong, Heejin Kim, Matthew J Maurer, Guo-Chang Zhang, Dairong Peng, Na Wei, Adam P Arkin, Yong-Su Jin
Many desired phenotypes for producing cellulosic biofuels are often observed in industrial Saccharomyces cerevisiae strains. However, many industrial yeast strains are polyploid and have low spore viability, making it difficult to use these strains for metabolic engineering applications. We selected the polyploid industrial strain S. cerevisiae ATCC 4124 exhibiting rapid glucose fermentation capability, high ethanol productivity, strong heat and inhibitor tolerance in order to construct an optimal yeast strain for producing cellulosic ethanol...
February 16, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28212815/systematic-testing-of-enzyme-perturbation-sensitivities-via-graded-dcas9-modulation-in-saccharomyces-cerevisiae
#10
Matthew Deaner, Hal S Alper
Dissecting genotype-phenotype relationships in a high-throughput and scalable manner is still an unresolved problem facing metabolic engineers. While the RNA-guided nuclease Cas9 has been repurposed as a programmable transcription regulator, its application has typically been limited to binary on/off regulation and thus misses informative and potentially optimal intermediate levels of gene expression. In this work, we establish a rapid method for fine-tuned, graded expression of pathway enzymes via dCas9 regulation by varying sgRNA target location as the dominant parameter...
February 14, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28232033/improvement-of-succinate-production-by-release-of-end-product-inhibition-in-corynebacterium-glutamicum
#11
Soon-Chun Chung, Joon-Song Park, Jiae Yun, Jin Hwan Park
Succinate is a renewable-based platform chemical that may be used to produce a wide range of chemicals including 1,4-butanediol, tetrahydrofurane, and γ-butyrolactone. However, industrial fermentation of organic acids is often subject to end-product inhibition, which significantly retards cell growth and limits metabolic activities and final productivity. In this study, we report the development of metabolically engineered Corynebacterium glutamicum for high production of succinate by release of end-product inhibition coupled with an increase of key metabolic flux...
February 13, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28215518/rational-engineering-of-diol-dehydratase-enables-1-4-butanediol-biosynthesis-from-xylose
#12
Jia Wang, Rachit Jain, Xiaolin Shen, Xinxiao Sun, Mengyin Cheng, James C Liao, Qipeng Yuan, Yajun Yan
Establishing novel synthetic routes for microbial production of chemicals often requires overcoming pathway bottlenecks by tailoring enzymes to enhance bio-catalysis or even achieve non-native catalysis. Diol dehydratases have been extensively studied for their interactions with C2 and C3 diols. However, attempts on utilizing these insights to enable catalysis on non-native substrates with more than two hydroxyl groups have been plagued with low efficiencies. Here, we rationally engineered the Klebsiella oxytoca diol dehydratase to enable and enhance catalytic activity toward a non-native C4 triol, 1,2,4-butanetriol...
February 13, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28192215/review-of-metabolic-pathways-activated-in-cancer-cells-as-determined-through-isotopic-labeling-and-network-analysis
#13
REVIEW
Wentao Dong, Mark A Keibler, Gregory Stephanopoulos
Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism...
February 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28188893/ultra-deep-next-generation-mitochondrial-genome-sequencing-reveals-widespread-heteroplasmy-in-chinese-hamster-ovary-cells
#14
Paul S Kelly, Colin Clarke, Alan Costello, Craig Monger, Justine Meiller, Heena Dhiman, Nicole Borth, Michael J Betenbaugh, Martin Clynes, Niall Barron
Recent sequencing of the Chinese hamster ovary (CHO) cell and Chinese hamster genomes has dramatically advanced our ability to understand the biology of these mammalian cell factories. In this study, we focus on the powerhouse of the CHO cell, the mitochondrion. Utilizing a high-resolution next generation sequencing approach we sequenced the Chinese hamster mitochondrial genome for the first time and surveyed the mutational landscape of CHO cell mitochondrial DNA (mtDNA). Depths of coverage ranging from ~3,319X to 8,056X enabled accurate identification of low frequency mutations (>1%), revealing that mtDNA heteroplasmy is widespread in CHO cells...
February 8, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28163219/probing-the-metabolic-phenotype-of-breast-cancer-cells-by-multiple-tracer-stable-isotope-resolved-metabolomics
#15
Andrew N Lane, Julie Tan, Yali Wang, Jun Yan, Richard M Higashi, Teresa W-M Fan
Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using (13)C6-glucose, (13)C-1+2-glucose, (13)C5,(15)N2-Gln, (13)C3-glycerol, and (13)C8-octanoate as tracers...
February 2, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28159643/metabolic-flexibility-of-a-butyrate-pathway-mutant-of-clostridium-acetobutylicum
#16
Minyeong Yoo, Christian Croux, Isabelle Meynial-Salles, Philippe Soucaille
Clostridium acetobutylicum possesses two homologous buk genes, buk (or buk1) and buk2, which encode butyrate kinases involved in the last step of butyrate formation. To investigate the contribution of buk in detail, an in-frame deletion mutant was constructed. However, in all the Δbuk mutants obtained, partial deletions of the upstream ptb gene were observed, and low phosphotransbutyrylase and butyrate kinase activities were measured. This demonstrates that i) buk (CA_C3075) is the key butyrate kinase-encoding gene and that buk2 (CA_C1660) that is poorly transcribed only plays a minor role; and ii) strongly suggests that a Δbuk mutant is not viable if the ptb gene is not also inactivated, probably due to the accumulation of butyryl-phosphate, which might be toxic for the cell...
January 31, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28122259/application-of-13-c-flux-analysis-to-identify-high-productivity-cho-metabolic-phenotypes
#17
Neil Templeton, Kevin D Smith, Allison G McAtee-Pereira, Haimanti Dorai, Michael J Betenbaugh, Steven E Lang, Jamey D Young
Industrial bioprocesses place high demands on the energy metabolism of host cells to meet biosynthetic requirements for maximal protein expression. Identifying metabolic phenotypes that promote high expression is therefore a major goal of the biotech industry. We conducted a series of (13)C flux analysis studies to examine the metabolic response to IgG expression during early stationary phase of CHO cell cultures grown in 3L fed-batch bioreactors. We examined eight clones expressing four different IgGs and compared with three non-expressing host-cell controls...
January 23, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28119139/towards-improved-butanol-production-through-targeted-genetic-modification-of-clostridium-pasteurianum
#18
Katrin M Schwarz, Alexander Grosse-Honebrink, Kamila Derecka, Carlo Rotta, Ying Zhang, Nigel P Minton
Declining fossil fuel reserves, coupled with environmental concerns over their continued extraction and exploitation have led to strenuous efforts to identify renewable routes to energy and fuels. One attractive option is to convert glycerol, a by-product of the biodiesel industry, into n-butanol, an industrially important chemical and potential liquid transportation fuel, using Clostridium pasteurianum. Under certain growth conditions this Clostridium species has been shown to predominantly produce n-butanol, together with ethanol and 1,3-propanediol, when grown on glycerol...
January 22, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28111249/metabolic-engineering-of-clostridium-autoethanogenum-for-selective-alcohol-production
#19
Fungmin Liew, Anne M Henstra, Michael Kӧpke, Klaus Winzer, Sean D Simpson, Nigel P Minton
Gas fermentation using acetogenic bacteria such as Clostridium autoethanogenum offers an attractive route for production of fuel ethanol from industrial waste gases. Acetate reduction to acetaldehyde and further to ethanol via an aldehyde: ferredoxin oxidoreductase (AOR) and alcohol dehydrogenase has been postulated alongside the classic pathway of ethanol formation via a bi-functional aldehyde/alcohol dehydrogenase (AdhE). Here we demonstrate that AOR is critical to ethanol formation in acetogens and inactivation of AdhE led to consistently enhanced autotrophic ethanol production (up to 180%)...
January 19, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28111248/improving-key-enzyme-activity-in-phenylpropanoid-pathway-with-a-designed-biosensor
#20
Dandan Xiong, Shikun Lu, Jieyuan Wu, Chaoning Liang, Wei Wang, Wenzhao Wang, Jian-Ming Jin, Shuang-Yan Tang
Overexpressing key enzymes of biosynthetic pathways for overproduction of value-added products usually imposes metabolic burdens on cells, which can be circumvented by improving the key enzyme activities. p-Coumarate: CoA ligase (4CL) is a critical enzyme in the phenylpropanoid pathway that synthesizes various natural products. To screen for 4CL with improved activity, a biosensor of resveratrol whose biosynthetic pathway involves 4CL was designed by engineering the TtgR regulatory protein. The biosensor exhibited good specificity and robustness, allowing rapid and sensitive selection of resveratrol hyper-producers...
January 19, 2017: Metabolic Engineering
journal
journal
33107
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"