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1

Moreno-Sánchez, Rafael, Emma Saavedra, Sara Rodríguez-Enríquez, and Viridiana Olín-Sandoval. "Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways." Journal of Biomedicine and Biotechnology 2008 (2008): 1–30. http://dx.doi.org/10.1155/2008/597913.

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The traditional experimental approaches used for changing the flux or the concentration of a particular metabolite of a metabolic pathway have been mostly based on the inhibition or over-expression of the presumed rate-limiting step. However, the attempts to manipulate a metabolic pathway by following such approach have proved to be unsuccessful. Metabolic Control Analysis (MCA) establishes how to determine, quantitatively, the degree of control that a given enzyme exerts on flux and on the concentration of metabolites, thus substituting the intuitive, qualitative concept of rate limiting step
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Marchesi, Federica, Debora Vignali, Beatrice Manini, Alessandra Rigamonti, and Paolo Monti. "Manipulation of Glucose Availability to Boost Cancer Immunotherapies." Cancers 12, no. 10 (2020): 2940. http://dx.doi.org/10.3390/cancers12102940.

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The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathw
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TEATHER, RON M. "APPLICATION OF GENE MANIPULATION TO RUMEN MICROFLORA." Canadian Journal of Animal Science 65, no. 3 (1985): 563–74. http://dx.doi.org/10.4141/cjas85-067.

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The potential impact of genetic manipulation of microorganisms has been fundamentally altered by the development of gene cloning and DNA synthesis techniques. Classical microbial biochemistry and genetics provided a rationale and methodology for the development of industrial fermentations in which an existing metabolic pathway of an organism could be exploited, directing a major part of the organism's synthetic capacity toward the production of a desired end product. Strains developed for these purposes, however, are able to survive only under controlled conditions in which competition from no
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Nouwen, Lonneke V., and Bart Everts. "Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape." Cells 9, no. 1 (2020): 161. http://dx.doi.org/10.3390/cells9010161.

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Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role
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Hayashi, Shunya, Mutsumi Watanabe, Makoto Kobayashi, Takayuki Tohge, Takashi Hashimoto, and Tsubasa Shoji. "Genetic Manipulation of Transcriptional Regulators Alters Nicotine Biosynthesis in Tobacco." Plant and Cell Physiology 61, no. 6 (2020): 1041–53. http://dx.doi.org/10.1093/pcp/pcaa036.

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Abstract The toxic alkaloid nicotine is produced in the roots of Nicotiana species and primarily accumulates in leaves as a specialized metabolite. A series of metabolic and transport genes involved in the nicotine pathway are coordinately upregulated by a pair of jasmonate-responsive AP2/ERF-family transcription factors, NtERF189 and NtERF199, in the roots of Nicotiana tabacum (tobacco). In this study, we explored the potential of manipulating the expression of these transcriptional regulators to alter nicotine biosynthesis in tobacco. The transient overexpression of NtERF189 led to alkaloid
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Ananga, Anthony, Vasil Georgiev, and Violeta Tsolova. "Manipulation and Engineering of Metabolic and Biosynthetic Pathway of Plant Polyphenols." Current Pharmaceutical Design 19, no. 34 (2013): 6186–206. http://dx.doi.org/10.2174/1381612811319340011.

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Ajaz, Saima, Mark J. McPhail, Keshav K. Singh, et al. "Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood mononuclear cells of patients with COVID-19." American Journal of Physiology-Cell Physiology 320, no. 1 (2021): C57—C65. http://dx.doi.org/10.1152/ajpcell.00426.2020.

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The COVID-19 pandemic has been the primary global health issue since its outbreak in December 2019. Patients with metabolic syndrome suffer from severe complications and a higher mortality rate due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We recently proposed that SARS-CoV-2 can hijack host mitochondrial function and manipulate metabolic pathways for their own advantage. The aim of the current study was to investigate functional mitochondrial changes in live peripheral blood mononuclear cells (PBMCs) from patients with COVID-19 and to decipher the pathways of
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Clark, Teresa J., Longyun Guo, John Morgan, and Jorg Schwender. "Modeling Plant Metabolism: From Network Reconstruction to Mechanistic Models." Annual Review of Plant Biology 71, no. 1 (2020): 303–26. http://dx.doi.org/10.1146/annurev-arplant-050718-100221.

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Mathematical modeling of plant metabolism enables the plant science community to understand the organization of plant metabolism, obtain quantitative insights into metabolic functions, and derive engineering strategies for manipulation of metabolism. Among the various modeling approaches, metabolic pathway analysis can dissect the basic functional modes of subsections of core metabolism, such as photorespiration, and reveal how classical definitions of metabolic pathways have overlapping functionality. In the many studies using constraint-based modeling in plants, numerous computational tools
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Ramos, J., A. Wasserfallen, K. Rose, and K. Timmis. "Redesigning metabolic routes: manipulation of TOL plasmid pathway for catabolism of alkylbenzoates." Science 235, no. 4788 (1987): 593–96. http://dx.doi.org/10.1126/science.3468623.

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Fornazier, Ricardo Francisco, Ricardo Antunes Azevedo, Renato Rodrigues Ferreira, and Vanderlei Aparecido Varisi. "Lysine catabolism: flow, metabolic role and regulation." Brazilian Journal of Plant Physiology 15, no. 1 (2003): 9–18. http://dx.doi.org/10.1590/s1677-04202003000100002.

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Lysine is an essential amino acid, synthesized in plants in the aspartic acid pathway. The lysine catabolism is performed by the action of two consecutive enzymes, lysine 2-oxoglutarate reductase (LOR) and saccharopine dehydrogenase (SDH). The steady state of lysine is controlled by both, synthesis and catabolism rates, with the final soluble lysine concentration in cereal seeds a direct result of these processes. In the last 40 years, the enzymes involved in lysine biosynthesis have been purified and characterized from some plant species such as carrot, maize, barley, rice, and coix. Recent r
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Jiménez, Alberto, María A. Santos, Markus Pompejus, and José L. Revuelta. "Metabolic Engineering of the Purine Pathway for Riboflavin Production in Ashbya gossypii." Applied and Environmental Microbiology 71, no. 10 (2005): 5743–51. http://dx.doi.org/10.1128/aem.71.10.5743-5751.2005.

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ABSTRACT Purine nucleotides are essential precursors for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and the biosynthesis of several amino acids and vitamins such as riboflavin. GTP is the immediate precursor for riboflavin biosynthesis, and its formation through the purine pathway is subject to several regulatory mechanisms in different steps. Extracellular purines repress the transcription of most genes required for de novo ATP and GTP synthesis. Additionally, three enzymes of the pathway, phosphoribosyl pyrophosphate
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12

Hädicke, Oliver, and Steffen Klamt. "Manipulation of the ATP pool as a tool for metabolic engineering." Biochemical Society Transactions 43, no. 6 (2015): 1140–45. http://dx.doi.org/10.1042/bst20150141.

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Cofactor engineering has been long identified as a valuable tool for metabolic engineering. Besides interventions targeting the pools of redox cofactors, many studies addressed the adenosine pools of microorganisms. In this mini-review, we discuss interventions that manipulate the availability of ATP with a special focus on ATP wasting strategies. We discuss the importance to fine-tune the ATP yield along a production pathway to balance process performance parameters like product yield and volumetric productivity.
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Thacker, Bryan E., and Susan T. Sharfstein. "Metabolic engineering of mammalian cells to produce heparan sulfates." Emerging Topics in Life Sciences 2, no. 3 (2018): 443–52. http://dx.doi.org/10.1042/etls20180007.

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Heparan sulfate (HS) is a glycosaminoglycan produced by all mammalian cells that plays important roles in physiology and various pathologies. Heparin is a highly sulfated form of HS that is used clinically as an anticoagulant. Heparin and HSs may also have therapeutic benefits for a wide variety of other indications. Cultured mammalian cells produce HS and, through genetic modification, have been used to elucidate the biosynthetic pathway. Recently, metabolic engineering has been used to produce HS from cultured mammalian cells for clinical purposes. This review describes the HS biosynthetic p
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York, Autumn, Joseph Argus, Anjie Zhen, et al. "Reprogramming lipid metabolism primes host antiviral immunity (INM7P.431)." Journal of Immunology 192, no. 1_Supplement (2014): 123.9. http://dx.doi.org/10.4049/jimmunol.192.supp.123.9.

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Abstract Oxysterols, or oxidized derivatives of cholesterol, have emerged as important regulators of adaptive and innate immunity. However, the molecular mechanisms by which these lipids facilitate host defense remain indeterminate. To better understand how cellular sterol metabolism influences innate immunity, we have generated gain- and loss-of-function macrophages that have key components of sterol homeostasis perturbed. Remarkably, we find that genetic manipulation of sterol biosynthetic capacity, and cellular sterol homeostasis, intrinsically alters its innate immune program. Genetic inhi
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Tian, Guimei, Linchun Jin, Devshri Doshi, et al. "TAMI-27. METABOLIC MANIPULATION OF T CELLS TO TREAT BRAIN TUMORS." Neuro-Oncology 23, Supplement_6 (2021): vi203—vi204. http://dx.doi.org/10.1093/neuonc/noab196.811.

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Abstract INTRODUCTION Glioblastoma are a challenge for neuro-oncologists and current therapies are minimally effective. Standard-of- care treatment is almost inevitably followed by disease recurrence. Adoptive T cell transfer has emerged as a viable therapeutic for brain malignancies. While promising, the efficacy of this approach is often limited by a complex immunosuppressive tumor microenvironment. These complexities mean that more sophisticated T cell products are required. OBJECTIVES The brain tumor microenvironment provides local restraints via metabolic competition suppressing antitumor
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Vieira, Vítor, and Miguel Rocha. "CoBAMP: a Python framework for metabolic pathway analysis in constraint-based models." Bioinformatics 35, no. 24 (2019): 5361–62. http://dx.doi.org/10.1093/bioinformatics/btz598.

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Abstract Summary CoBAMP is a modular framework for the enumeration of pathway analysis concepts, such as elementary flux modes (EFM) and minimal cut sets in genome-scale constraint-based models (CBMs) of metabolism. It currently includes the K-shortest EFM algorithm and facilitates integration with other frameworks involving reading, manipulation and analysis of CBMs. Availability and implementation The software is implemented in Python 3, supported on most operating systems and requires a mixed-integer linear programming optimizer supported by the optlang framework. Source-code is available a
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17

'Amirah, Baharin, Abdullah Afnizanfaizal, and Noorain Mohmad Yousoff Siti. "Prediction of Bioprocess Production Using Deep Neural Network Method." TELKOMNIKA Telecommunication, Computing, Electronics and Control 15, no. 2 (2017): 805–13. https://doi.org/10.12928/TELKOMNIKA.v15i2.6124.

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Deep learning enhanced the state-of-the-art methods in genomics allows it to be used in analysing the biological data with high prediction. The training process of neural network with several hidden layers which has been facilitated by deep learning has been subjected into increased interest in achieving remarkable results in various fields. Thus, the extraction of bioprocess production can be implemented by pathway prediction in genomic metabolic network in eschericia coli. As metabolic engineering involves the manipulation of genes which have the potential to increase the yield of metabolite
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18

LE GOFFE, Claire, Geneviève VALLETTE, Anne JARRY, Chantal BOU-HANNA, and Christian L. LABOISSE. "The in vitro manipulation of carbohydrate metabolism: a new strategy for deciphering the cellular defence mechanisms against nitric oxide attack." Biochemical Journal 344, no. 3 (1999): 643–48. http://dx.doi.org/10.1042/bj3440643.

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This study was aimed at examining the effects of manipulating the carbohydrate source of the culture medium on the cellular sensitivity of epithelial cells to an oxidative attack. Our rationale was that substituting galactose for glucose in culture media would remove the protection afforded by glucose utilization in two major metabolic pathways, i.e. anaerobic glycolysis and/or the pentose phosphate pathway (PPP), which builds up cellular reducing power. Indeed, we show that the polarized human colonic epithelial cell line HT29-Cl.16E was sensitive to the deleterious effects of the NO donor PA
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19

Lee, Young-Joon, and Jae-Yong Cho. "Genetic manipulation of a primary metabolic pathway for l-ornithine production in Escherichia coli." Biotechnology Letters 28, no. 22 (2006): 1849–56. http://dx.doi.org/10.1007/s10529-006-9163-y.

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20

Eisenreich, Wolfgang, Julian Leberfing, Thomas Rudel, Jürgen Heesemann, and Werner Goebel. "Interactions of SARS-CoV-2 with Human Target Cells—A Metabolic View." International Journal of Molecular Sciences 25, no. 18 (2024): 9977. http://dx.doi.org/10.3390/ijms25189977.

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Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply o
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Li, Fanyue, Roypim Thananusak, Nachon Raethong, et al. "Dissecting Holistic Metabolic Acclimatization of Mucor circinelloides WJ11 Defective in Carotenoid Biosynthesis." Biology 13, no. 4 (2024): 276. http://dx.doi.org/10.3390/biology13040276.

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Mucor circinelloides WJ11 is a lipid-producing strain with industrial potential. A holistic approach using gene manipulation and bioprocessing development has improved lipid production and the strain’s economic viability. However, the systematic regulation of lipid accumulation and carotenoid biosynthesis in M. circinelloides remains unknown. To dissect the metabolic mechanism underlying lipid and carotenoid biosynthesis, transcriptome analysis and reporter metabolites identification were implemented between the wild-type (WJ11) and ΔcarRP WJ11 strains of M. circinelloides. As a result, transc
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WRIGHT, T. C., J. P. CANT, and B. W. MCBRIDE. "Use of metabolic control analysis in lactation biology." Journal of Agricultural Science 146, no. 3 (2008): 267–73. http://dx.doi.org/10.1017/s002185960800782x.

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SUMMARYSensitivity analysis is routinely carried out in the evaluation of simulation models to identify the degree to which parameters influence model outputs. This type of sensitivity analysis is much less frequently applied to real systems, but a technique called metabolic control analysis (MCA) was developed in the 1970s for the purpose of experimentally identifying the degree to which individual enzymes in a metabolic pathway influence flux through the pathway. MCA is applied to the results of inhibition, activation or genetic manipulation of enzymatic steps in a biochemical pathway. Flux
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Jimoh, Simiat, Issa, Sheriffdeen Bale, Fadiji, Oyinkansola Suliat, and Ebere, Christian Ugochukwu. "Metabolic Engineering of Saccharomyces cerevisiae for Enhanced Steroid Biosynthesis: Advances, Strategies, and Industrial Implications." Sahel Journal of Life Sciences FUDMA 3, no. 1 (2025): 538–45. https://doi.org/10.33003/sajols-2025-0301-65.

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Saccharomyces cerevisiae, an extensively studied model yeast has received significant attention largely due to its well-characterised genomic materials, ease of genetic manipulation, and usefulness in the production of steroidal compounds.. Steroids are essential molecules used extensively in pharmaceuticals, cosmetics, and agricultural industries. However, chemical synthesis and extraction techniques for steroids are often inefficient and environmentally taxing. Advances in metabolic engineering and synthetic biology have facilitated the reprogramming of Saccharomyces cerevisiae to enhance th
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Burgess, Shawn C., F. Mark H. Jeffrey, Charles Storey, et al. "Effect of murine strain on metabolic pathways of glucose production after brief or prolonged fasting." American Journal of Physiology-Endocrinology and Metabolism 289, no. 1 (2005): E53—E61. http://dx.doi.org/10.1152/ajpendo.00601.2004.

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Background strain is known to influence the way a genetic manipulation affects mouse phenotypes. Despite data that demonstrate variations in the primary phenotype of basic inbred strains of mice, there is limited data available about specific metabolic fluxes in vivo that may be responsible for the differences in strain phenotypes. In this study, a simple stable isotope tracer/NMR spectroscopic protocol has been used to compare metabolic fluxes in ICR, FVB/N (FVB), C57BL/6J (B6), and 129S1/SvImJ (129) mouse strains. After a short-term fast in these mice, there were no detectable differences in
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Ramesh, Parvathy, Satish Kumar Tiwari, Md Kaizer та ін. "The NF-κB Factor Relish maintains blood progenitor homeostasis in the developing Drosophila lymph gland". PLOS Genetics 20, № 9 (2024): e1011403. http://dx.doi.org/10.1371/journal.pgen.1011403.

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Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Usin
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Derntl, Christian, Daniel P. Kiesenhofer, Robert L. Mach, and Astrid R. Mach-Aigner. "Novel Strategies for Genomic Manipulation of Trichoderma reesei with the Purpose of Strain Engineering." Applied and Environmental Microbiology 81, no. 18 (2015): 6314–23. http://dx.doi.org/10.1128/aem.01545-15.

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ABSTRACTThe state-of-the-art procedure for gene insertions intoTrichoderma reeseiis a cotransformation of two plasmids, one bearing the gene of interest and the other a marker gene. This procedure yields up to 80% transformation efficiency, but both the number of integrated copies and the loci of insertion are unpredictable. This can lead to tremendous pleiotropic effects. This study describes the development of a novel transformation system for site-directed gene insertion based on auxotrophic markers. For this purpose, we tested the applicability of the genesasl1(encoding an enzyme of thel-a
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Su, Buli, Ming-Rong Deng, and Honghui Zhu. "Advances in the Discovery and Engineering of Gene Targets for Carotenoid Biosynthesis in Recombinant Strains." Biomolecules 13, no. 12 (2023): 1747. http://dx.doi.org/10.3390/biom13121747.

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Carotenoids are naturally occurring pigments that are abundant in the natural world. Due to their excellent antioxidant attributes, carotenoids are widely utilized in various industries, including the food, pharmaceutical, cosmetic industries, and others. Plants, algae, and microorganisms are presently the main sources for acquiring natural carotenoids. However, due to the swift progress in metabolic engineering and synthetic biology, along with the continuous and thorough investigation of carotenoid biosynthetic pathways, recombinant strains have emerged as promising candidates to produce car
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Auvinen, Juha, Joona Tapio, Ville Karhunen, et al. "Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia." Science Advances 7, no. 29 (2021): eabi4822. http://dx.doi.org/10.1126/sciadv.abi4822.

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Activation of the hypoxia-inducible factor (HIF) pathway reprograms energy metabolism. Hemoglobin (Hb) is the main carrier of oxygen. Using its normal variation as a surrogate measure for hypoxia, we explored whether lower Hb levels could lead to healthier metabolic profiles in mice and humans (n = 7175) and used Mendelian randomization (MR) to evaluate potential causality (n = 173,480). The results showed evidence for lower Hb levels being associated with lower body mass index, better glucose tolerance and other metabolic profiles, lower inflammatory load, and blood pressure. Expression of th
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Yang, Huang-Yu, Chao-Yi Wu, Jia-Jin Chen, and Tao-Han Lee. "Treatment Strategies and Metabolic Pathway Regulation in Urothelial Cell Carcinoma: A Comprehensive Review." International Journal of Molecular Sciences 21, no. 23 (2020): 8993. http://dx.doi.org/10.3390/ijms21238993.

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For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associat
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Singleton, K. D., N. Serkova, and P. E. Wischmeyer. "GLUTAMINE ATTENUATES THE METABOLIC DYSFUNCTION OF SUBLETHAL ENDOTOXIN SHOCK VIA MANIPULATION OF THE HEAT STRESS PROTEIN PATHWAY." Shock 19, Supplement (2003): 29–30. http://dx.doi.org/10.1097/00024382-200306001-00086.

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31

Jeong, Euna, Masao Nagasaki, Ayumu Saito, and Satoru Miyano. "Cell System Ontology: Representation for Modeling, Visualizing, and Simulating Biological Pathways." In Silico Biology: Journal of Biological Systems Modeling and Multi-Scale Simulation 7, no. 6 (2007): 623–38. https://doi.org/10.3233/isi-2007-00335.

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With the rapidly accumulating knowledge of biological entities and networks, there is a growing need for a general framework to understand this information at a system level. In order to understand life as system, a formal description of system dynamics with semantic validation will be necessary. Within the context of biological pathways, several formats have been proposed, e.g., SBML, CellML, and BioPAX. Unfortunately, these formats lack the formal definitions of each term or fail to capture the system dynamics behavior. Thus, we have developed a new system dynamics centered ontology called C
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32

Wang, Qiong, and Michael J. Betenbaugh. "Metabolic engineering of CHO cells to prepare glycoproteins." Emerging Topics in Life Sciences 2, no. 3 (2018): 433–42. http://dx.doi.org/10.1042/etls20180056.

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As a complex and common post-translational modification, N-linked glycosylation affects a recombinant glycoprotein's biological activity and efficacy. For example, the α1,6-fucosylation significantly affects antibody-dependent cellular cytotoxicity and α2,6-sialylation is critical for antibody anti-inflammatory activity. Terminal sialylation is important for a glycoprotein's circulatory half-life. Chinese hamster ovary (CHO) cells are currently the predominant recombinant protein production platform, and, in this review, the characteristics of CHO glycosylation are summarized. Moreover, recent
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Kemper, Katarina, Max Hirte, Markus Reinbold, Monika Fuchs, and Thomas Brück. "Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems." Beilstein Journal of Organic Chemistry 13 (May 8, 2017): 845–54. http://dx.doi.org/10.3762/bjoc.13.85.

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With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isop
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Deji-Oloruntoba, Opeyemi O., Taiwo O. Elufioye, Stephen Adeniyi Adefegha, and Miran Jang. "Can Caenorhabditis elegans Serve as a Reliable Model for Drug and Nutraceutical Discovery?" Applied Biosciences 4, no. 2 (2025): 23. https://doi.org/10.3390/applbiosci4020023.

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Experimental research demands the selection of appropriate models to align with study objectives and conditions. Traditional experimental models, such as in vivo animal studies and in vitro systems like organoids, present nutraceutical and pharmaceutical research limitations such as high cost, ethical concerns, long lifespan, and difficult genetic manipulation. Caenorhabditis elegans has proved to be a valuable model as a result of its genetic and physiological similarities to higher organisms, fully sequenced genome, short life cycle, and transparency. These features enable high-throughput sc
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Vieira, Vítor, Paulo Maia, Miguel Rocha, and Isabel Rocha. "Comparison of pathway analysis and constraint-based methods for cell factory design." BMC Bioinformatics 20, no. 1 (2019): 350. https://doi.org/10.1186/s12859-019-2934-y.

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<strong>Background: </strong>Computational strain optimisation methods (CSOMs) have been successfully used to exploit genome-scale metabolic models, yielding strategies useful for allowing compound overproduction in metabolic cell factories. Minimal cut sets are particularly interesting since their definition allows searching for intervention strategies that impose strong growth-coupling phenotypes, and are not subject to optimality bias when compared with simulation-based CSOMs. However, since both types of methods have different underlying principles, they also imply different ways to formul
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Jo, Yeong Deuk, Jaihyunk Ryu, Ye-Sol Kim, et al. "Dramatic Increase in Content of Diverse Flavonoids Accompanied with Down-Regulation of F-Box Genes in a Chrysanthemum (Chrysanthemum × morifolium (Ramat.) Hemsl.) Mutant Cultivar Producing Dark-Purple Ray Florets." Genes 11, no. 8 (2020): 865. http://dx.doi.org/10.3390/genes11080865.

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Anthocyanins (a subclass of flavonoids) and flavonoids are crucial determinants of flower color and substances of pharmacological efficacy, respectively, in chrysanthemum. However, metabolic and transcriptomic profiling regarding flavonoid accumulation has not been performed simultaneously, thus the understanding of mechanisms gained has been limited. We performed HPLC-DAD-ESI-MS (high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization mass spectrometry) and transcriptome analyses using “ARTI-Dark Chocolate” (AD), which is a chrysanthemum muta
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Shianiou, Gavriella, Savvas Teloni, and Yiorgos Apidianakis. "Intestinal Immune Deficiency and Juvenile Hormone Signaling Mediate a Metabolic Trade-off in Adult Drosophila Females." Metabolites 13, no. 3 (2023): 340. http://dx.doi.org/10.3390/metabo13030340.

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A trade-off hypothesis pertains to the biased allocation of limited resources between two of the most important fitness traits, reproduction and survival to infection. This quid pro quo manifests itself within animals prioritizing their energetic needs according to genetic circuits balancing metabolism, germline activity and immune response. Key evidence supporting this hypothesis includes dipteran fecundity being compromised by systemic immunity, and female systemic immunity being compromised by mating. Here, we reveal a local trade-off taking place in the female Drosophila midgut upon immune
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Mirgayazova, Regina, Raniya Khadiullina, Vitaly Chasov, et al. "Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?" Genes 11, no. 6 (2020): 704. http://dx.doi.org/10.3390/genes11060704.

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The TP53 gene encodes the transcription factor and oncosuppressor p53 protein that regulates a multitude of intracellular metabolic pathways involved in DNA damage repair, cell cycle arrest, apoptosis, and senescence. In many cases, alterations (e.g., mutations of the TP53 gene) negatively affect these pathways resulting in tumor development. Recent advances in genome manipulation technologies, CRISPR/Cas9, in particular, brought us closer to therapeutic gene editing for the treatment of cancer and hereditary diseases. Genome-editing therapies for blood disorders, blindness, and cancer are cur
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39

Broughton, Susan, and Linda Partridge. "Insulin/IGF-like signalling, the central nervous system and aging." Biochemical Journal 418, no. 1 (2009): 1–12. http://dx.doi.org/10.1042/bj20082102.

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Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundi
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40

Wungsintaweekul, Juraithip, Chutima Sriyapai, Sanlaya Kaewkerd, Supinya Tewtrakul, Damrong Kongduang, and Wanchai De-Eknamkul. "Establishment of Croton stellatopilosus Suspension Culture for Geranylgeraniol Production and Diterpenoid Biosynthesis." Zeitschrift für Naturforschung C 62, no. 5-6 (2007): 389–96. http://dx.doi.org/10.1515/znc-2007-5-612.

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Diterpenoids in higher plants are biosynthesized from isoprene units obtained from two distinct pathways: the mevalonate pathway and the deoxyxylulose phosphate pathway. The metabolic partitioning of both pathways in plant species is dependent upon the type of culture. In order to study the diterpenoid biosynthesis in Croton stellatopilosus cell culture, callus culture was firstly induced from C. stellatopilosus young leaves in Murashige and Skoog (MS) medium in the presence of 1.0 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D), 1.0 mg/l benzyladenine (BA), 3% (w/v) sucrose and 0.8% (w/v) agar. T
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41

Wieloch, Thomas, Thomas David Sharkey, Roland Anton Werner, and Jürgen Schleucher. "Intramolecular carbon isotope signals reflect metabolite allocation in plants." Journal of Experimental Botany 73, no. 8 (2022): 2558–75. http://dx.doi.org/10.1093/jxb/erac028.

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Abstract Stable isotopes at natural abundance are key tools to study physiological processes occurring outside the temporal scope of manipulation and monitoring experiments. Whole-molecule carbon isotope ratios (13C/12C) enable assessments of plant carbon uptake yet conceal information about carbon allocation. Here, we identify an intramolecular 13C/12C signal at tree-ring glucose C-5 and C-6 and develop experimentally testable theories on its origin. More specifically, we assess the potential of processes within C3 metabolism for signal introduction based (inter alia) on constraints on signal
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Jaramillo-Madrid, Ana Cristina, Raffaela Abbriano, Justin Ashworth, Michele Fabris, Mathieu Pernice, and Peter J. Ralph. "Overexpression of Key Sterol Pathway Enzymes in Two Model Marine Diatoms Alters Sterol Profiles in Phaeodactylum tricornutum." Pharmaceuticals 13, no. 12 (2020): 481. http://dx.doi.org/10.3390/ph13120481.

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Sterols are a class of triterpenoid molecules with diverse functional roles in eukaryotic cells, including intracellular signaling and regulation of cell membrane fluidity. Diatoms are a dominant eukaryotic phytoplankton group that produce a wide diversity of sterol compounds. The enzymes 3-hydroxy-3-methyl glutaryl CoA reductase (HMGR) and squalene epoxidase (SQE) have been reported to be rate-limiting steps in sterol biosynthesis in other model eukaryotes; however, the extent to which these enzymes regulate triterpenoid production in diatoms is not known. To probe the role of these two metab
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Anwar, Muhammad, Jingkai Wang, Jiancheng Li, Muhammad Mohsin Altaf, and Zhangli Hu. "MYB Transcriptional Factors Affects Upstream and Downstream MEP Pathway and Triterpenoid Biosynthesis in Chlamydomonas reinhardtii." Processes 12, no. 3 (2024): 487. http://dx.doi.org/10.3390/pr12030487.

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Terpenoids are enormous and different types of naturally occurring metabolites playing an important role in industrial applications. Cost-effective and sustainable production of terpenoids at commercial scale is the big challenge because of its low abundance from their natural sources. Metabolic and genetic engineering in microorganisms provide the ideal platform for heterologous overexpression protein systems. The photosynthetic green alga Chlamydomonas reinhardtii is considered as a model host for the production of economic and sustainable terpenoids, but the regulation mechanism of their me
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Carpenter, Evan L., Alyssa L. Becker, and Arup K. Indra. "NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation." Cancers 14, no. 6 (2022): 1531. http://dx.doi.org/10.3390/cancers14061531.

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Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g., keratinocytes). However, melanocytes encounter a large burden of oxidative stress during this process, due to both exogenous and endogenous sources. Therefore, melanocytes employ numerous antioxidant defenses to protect themselves; these a
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Leal, Helena, João Cardoso, Patrícia Valério, et al. "SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway." International Journal of Molecular Sciences 23, no. 12 (2022): 6790. http://dx.doi.org/10.3390/ijms23126790.

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Nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with obesity and insulin resistance, is characterized by hepatic lipid accumulation and activation of the endoplasmic reticulum (ER) stress response. The sirtuin 2 (SIRT2) protein deacetylase is emerging as a new player in metabolic homeostasis, but its role in the development of hepatic steatosis and its link with ER stress activation remains unknown. SIRT2-knockout (SIRT2-KO) and wild-type mice were fed either a control or a high-fat diet (HFD) for 4 weeks. Genetic manipulation of SIRT2 levels was performed in human he
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Sun, Wenhui, Bo Jiang, Dongying Zhao, Zhongji Pu, and Yongming Bao. "Integration of metabolic pathway manipulation and promoter engineering for the fine‐tuned biosynthesis of malic acid in Bacillus coagulans." Biotechnology and Bioengineering 118, no. 7 (2021): 2597–608. http://dx.doi.org/10.1002/bit.27780.

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Yu, Le-Yi, Lin-Xiang Li, Lin-Lin Yao, Jun-Wei Zheng, Bin Wang, and Li Pan. "A Special Phenotype of Aconidial Aspergillus niger SH2 and Its Mechanism of Formation via CRISPRi." Journal of Fungi 8, no. 7 (2022): 679. http://dx.doi.org/10.3390/jof8070679.

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The complex morphological structure of Aspergillus niger influences its production of proteins, metabolites, etc., making the genetic manipulation and clonal purification of this species increasingly difficult, especially in aconidial Aspergillus niger. In this study, we found that N-acetyl-D-glucosamine (GlcNAc) could induce the formation of spore-like propagules in the aconidial Aspergillus niger SH2 strain. The spore-like propagules possessed life activities such as drug resistance, genetic transformation, and germination. Transcriptomic analysis indicated that the spore-like propagules wer
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48

Ma, Gary S., Inmaculada Lopez-Sanchez, Nicolas Aznar, et al. "Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity." Molecular Biology of the Cell 26, no. 23 (2015): 4209–23. http://dx.doi.org/10.1091/mbc.e15-08-0553.

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Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Gαi, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as
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Dowdy, Tyrone, Lumin Zhang, Orieta Celiku, et al. "DDRE-20. TARGETING SPHINGOLIPID PATHWAY REVEALS VULNERABILITY IN IDH1MUT GLIOMA." Neuro-Oncology Advances 3, Supplement_1 (2021): i10. http://dx.doi.org/10.1093/noajnl/vdab024.042.

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Abstract BACKGROUND While central carbon metabolism has been studied extensively in cancer, lipidomic research is sparse. Sphingolipids participate in cellular functions including secondary messengers, lymphocyte trafficking, inflammation, angiogenesis, migration, proliferation, necrosis and apoptosis, thus highlighting the importance of understanding their role to tumor phenotype. Our investigation into metabolic alterations involving sphingolipid pathway in patient-derived IDH1mut glioma cultures aimed to identify points of metabolic vulnerability. METHODS Dysregulation of sphingolipid metab
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Fuchs, Lorenz K., Alistair H. Holland, Richard A. Ludlow, et al. "Genetic Manipulation of Biosynthetic Pathways in Mint." Frontiers in Plant Science 13 (June 14, 2022). http://dx.doi.org/10.3389/fpls.2022.928178.

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In recent years, the study of aromatic plants has seen an increase, with great interest from industrial, academic, and pharmaceutical industries. Among plants attracting increased attention are the Mentha spp. (mint), members of the Lamiaceae family. Mint essential oils comprise a diverse class of molecules known as terpenoids/isoprenoids, organic chemicals that are among the most diverse class of naturally plant derived compounds. The terpenoid profile of several Mentha spp. is dominated by menthol, a cyclic monoterpene with some remarkable biological properties that make it useful in the pha
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