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Metabolic engineering

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https://www.readbyqxmd.com/read/29349039/engineering-escherichia-coli-for-the-production-of-terpene-mixture-enriched-in-caryophyllene-and-caryophyllene-alcohol-as-potential-aviation-fuel-compounds
#1
Weihua Wu, Fang Liu, Ryan W Davis
Recent studies have revealed that caryophyllene and its stereoisomers not only exhibit multiple biological activities but also have desired properties as renewable candidates for ground transportation and jet fuel applications. This study presents the first significant production of caryophyllene and caryolan-1-ol by an engineered E. coli with heterologous expression of mevalonate pathway genes with a caryophyllene synthase and a caryolan-1-ol synthase. By optimizing metabolic flux and fermentation parameters, the engineered strains yielded 449 mg/L of total terpene, including 406 mg/L sesquiterpene with 100 mg/L caryophyllene and 10 mg/L caryolan-1-ol...
June 2018: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29348423/a-tissue-mimetic-nano-fibrillar-hybrid-injectable-hydrogel-for-potential-soft-tissue-engineering-applications
#2
Neda Latifi, Meisam Asgari, Hojatollah Vali, Luc Mongeau
While collagen type I (Col-I) is commonly used as a structural component of biomaterials, collagen type III (Col-III), another fibril forming collagen ubiquitous in many soft tissues, has not previously been used. In the present study, the novel concept of an injectable hydrogel with semi-interpenetrating polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was introduced as a component of the novel hydrogel, inspired by its co-presence with Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms of diameter and mechanics, and its established role in regulating scar formation...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346685/metabolic-flux-engineering-of-cembratrien-ol-production-in-both-the-glandular-trichome-and-leaf-mesophyll-in-nicotiana-tabacum
#3
Hongying Zhang, Songtao Zhang, Yongxia Yang, Hongfang Jia, Hong Cui
Cembratrien-ol synthase (CBTS) catalyses the first step in cembranoid biosynthesis, producing cembratrien-ols in plant trichomes. In our previous study, microarray transcriptomes between leaves with trichomes and leaves without trichomes showed that a NtCBTS2 gene was expressed exclusively and abundantly in trichomes. Here, two NtCBTS2 isogenes (NtCBTS2a and NtCBTS2b), derived from a diploid genome donor, N. sylvestris, were identified from N. tabacum. Both genes were expressed primarily in trichomes, with relatively decreased transcription in flowers and stems, faint expression in roots, and no expression was detected in leaves lacking trichomes...
January 15, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29346617/riboswitching-with-ciprofloxacin-development-and-characterization-of-a-novel-rna-regulator
#4
Florian Groher, Cristina Bofill-Bosch, Christopher Schneider, Johannes Braun, Sven Jager, Katharina Geißler, Kay Hamacher, Beatrix Suess
RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29344811/metabolic-evolution-and-a-comparative-omics-analysis-of-corynebacterium-glutamicum-for-putrescine-production
#5
Zhen Li, Yu-Ping Shen, Xuan-Long Jiang, Li-Shen Feng, Jian-Zhong Liu
Putrescine is widely used in the industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Because the highest titer of putrescine is much lower than that of its precursor L-ornithine reported in microorganisms to date, further work is needed to increase putrescine production in Corynebacterium glutamicum. We first compared 7 ornithine decarboxylase genes and found that the Enterobacter cloacae ornithine decarboxylase gene speC1 was most suitable for putrescine production in C. glutamicum...
January 17, 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29343065/perfect-adaptation-and-optimal-equilibrium-productivity-in-a-simple-microbial-biofuel-metabolic-pathway-using-dynamic-integral-control
#6
Corentin Briat, Mustafa H Khammash
The production of complex biomolecules by genetically engineered organisms is one of the most promising applications of metabolic engineering and synthetic biology. To obtain processes with high productivity, it is therefore crucial to design and implement efficient dynamic in-vivo regulation strategies. We consider here the microbial biofuel production model of Dunlop et al. (2010) for which we demonstrate that an antithetic dynamic integral control strategy can achieve robust perfect adaptation for the intracellular biofuel concentration in presence of poorly known network parameters and implementation errors in certain rate parameters of the controller...
January 17, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29340876/biomaterials-and-regenerative-medicine-in-urology
#7
N F Davis, E M Cunnane, M R Quinlan, J J Mulvihill, N Lawrentschuk, D M Bolton, M T Walsh
Autologous gastrointestinal tissue is the gold standard biomaterial for urinary tract reconstruction despite its long-term neuromechanical and metabolic complications. Regenerative biomaterials have been proposed as alternatives; however many are limited by a poor host derived regenerative response and deficient supportive elements for effective tissue regeneration in vivo. Urological biomaterials are sub-classified into xenogenic extracellular matrices (ECMs) or synthetic polymers. ECMs are decellularised, biocompatible, biodegradable biomaterials derived from animal organs...
January 17, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29340710/production-of-plant-derived-polyphenols-in-microorganisms-current-state-and-perspectives
#8
REVIEW
Lars Milke, Jennifer Aschenbrenner, Jan Marienhagen, Nicolai Kallscheuer
Plants synthesize several thousand different polyphenols of which many have the potential to aid in preventing or treating cancer, cardiovascular, and neurodegenerative diseases. However, plants usually contain complex polyphenol mixtures impeding access to individual compounds in larger quantities. In contrast, functional integration of biosynthetic plant polyphenol pathways into microorganisms allows for the production of individual polyphenols as chemically distinct compounds, which can be synthesized in large amounts and can be more easily isolated...
January 16, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#9
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337138/let-7-suppresses-b-cell-activation-through-restricting-the-availability-of-necessary-nutrients
#10
Shuai Jiang, Wei Yan, Shizhen Emily Wang, David Baltimore
The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29335298/crystal-structure-of-ispf-from-bacillus-subtilis-and-absence-of-protein-complex-assembly-among-ispd-ispe-ispf-enzymes-in-the-mep-pathway
#11
Zhongchuan Liu, Yun Jin, Weifeng Liu, Yong Tao, Ganggang Wang
2-C-methyl-d-erythritol 2, 4-cyclodiphosphate synthase (IspF) is a key enzyme in the 2-C-Methyl-d-erythritol-4-phosphate (MEP) pathway of isoprenoid biosynthesis. This enzyme catalyzes the 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate (CDPME2P) to 2-C-methyl-d-erythritol 2, 4-cyclodiphosphate (MEcDP) with concomitant release of cytidine 5'-diphospate (cytosine monophosphate) (CMP). Bacillus subtilis is a potential host cell for the production of isoprenoids, but few studies are performed on the key enzymes of MEP pathway in B...
January 15, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29333115/clinical-significance-of-fluorine-18-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-in-the-follow-up-of-colorectal-cancer-searching-off-approaches-increasing-specificity-for-detection-of-recurrence
#12
Semra Ince, Kursat Okuyucu, Oguz Hancerliogulları, Engin Alagoz, Huseyin San, Nuri Arslan
Background: Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (l8F-FDG) positron emission tomography/computed tomography (PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of 18F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29331920/engineering-yeast-for-utilization-of-alternative-feedstocks
#13
REVIEW
Allison Yaguchi, Michael Spagnuolo, Mark Blenner
Realizing the economic benefits of alternative substrates for commodity chemical bioproduction typically requires significant metabolic engineering of common model organisms, such as Saccharomyces cerevisiae. A growing toolkit is enabling engineering of non-conventional yeast that have robust native metabolism for xylose, acetate, aromatics, and waste lipids. Scheffersomyces stipitis was engineered to produce itaconic acid from xylose. Yarrowia lipolytica produced lipids from dilute acetate at over 100g/L. Cutaneotrichosporon oleaginosus was engineered to produce omega-3 fatty acids and recently was shown to accumulate nearly 70% lipids when grown on aromatics as a carbon source...
January 10, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29331411/tailoring-cyanobacterial-cell-factory-for-improved-industrial-properties
#14
REVIEW
Guodong Luan, Xuefeng Lu
Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses...
January 10, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29331410/implementing-crispr-cas-technologies-in-conventional-and-non-conventional-yeasts-current-state-and-future-prospects
#15
REVIEW
Hana Raschmanova, Astrid Weninger, Anton Glieder, Karin Kovar, Thomas Vogl
Within five years, the CRISPR-Cas system has emerged as the dominating tool for genome engineering, while also changing the speed and efficiency of metabolic engineering in conventional (Saccharomyces cerevisiae and Schizosaccharomyces pombe) and non-conventional (Yarrowia lipolytica, Pichia pastoris syn. Komagataella phaffii, Kluyveromyces lactis, Candida albicans and C. glabrata) yeasts. Especially in S. cerevisiae, an extensive toolbox of advanced CRISPR-related applications has been established, including crisprTFs and gene drives...
January 10, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29331090/enhanced-chondrogenesis-of-mesenchymal-stem-cells-over-silk-fibroin-chitosan-chondroitin-sulfate-three-dimensional-scaffold-in-dynamic-culture-condition
#16
Parinita Agrawal, Krishna Pramanik, Varshini Vishwanath, Amit Biswas, Akalabya Bissoyi, Pradeep Kumar Patra
Chondroitin sulfate (Ch) is one of the main structural components of cartilage tissue, therefore, its presence in tissue engineered scaffold is expected to enhance cartilage regeneration. Previously, silk fibroin/chitosan (SF/CS) blend was proven to be a potential biomaterial for tissue development. In this study, the effect of Ch on physicochemical and biological properties of SF/CS blend was investigated and scaffolds with 0.8 wt% Ch was found to be favorable. The scaffolds possess pore size of 37-212 µm, contact angle 46...
January 13, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/29331057/manifestations-and-mechanisms-of-myocardial-lipotoxicity-in-obesity
#17
Arthur C Sletten, Linda R Peterson, Jean E Schaffer
Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is among the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodeling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29330665/a-synthetic-pathway-for-the-production-of-2-hydroxyisovaleric-acid-in-escherichia-coli
#18
Seokjung Cheong, James M Clomburg, Ramon Gonzalez
Synthetic biology, encompassing the design and construction of novel artificial biological pathways and organisms and the redesign of existing natural biological systems, is rapidly expanding the number of applications for which biological systems can play an integral role. In the context of chemical production, the combination of synthetic biology and metabolic engineering approaches continues to unlock the ability to biologically produce novel and complex molecules from a variety of feedstocks. Here, we utilize a synthetic approach to design and build a pathway to produce 2-hydroxyisovaleric acid in Escherichia coli and demonstrate how pathway design can be supplemented with metabolic engineering approaches to improve pathway performance from various carbon sources...
January 12, 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#19
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330181/a-novel-l-glutamate-exporter-of-corynebacterium-glutamicum
#20
Yu Wang, Guoqiang Cao, Deyu Xu, Liwen Fan, Xinyang Wu, Xiaomeng Ni, Shuxin Zhao, Ping Zheng, Jibin Sun, Yanhe Ma
Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyper-production of biochemicals using microbial cell factories. Identification and characterization of transporters are therefore of great significance for understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter MscCG2 that extensively exists in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter MscCG was discovered in an industrial l-glutamate producing C...
January 12, 2018: Applied and Environmental Microbiology
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