ABSTRACT
Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic research and China's competence in the area of metabolic engineering according to the data of papers published in SCI-indexed journals in the past 30 years. Subsequently, the article summarizes the development of systems biology methods and enabling technologies of synthetic biology and their applications in metabolic engineering in the past 10 years. Finally, the major challenges and future perspectives for the development of metabolic engineering are briefly discussed.
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Biotechnology , Industry , Metabolic Engineering , Synthetic Biology , Systems BiologyABSTRACT
Cerebrospinal fluid and level of blood S100B protein are significantly higher in patients with intracerebral hemorrhage,which are associated the differentiation of stroke,damage of blood-brain barrier,hematoma volume,brain edema,degree of nerve function defect,and outcomes.Therefore,S100B is expected to be used in the diagnosis of intracerebral hemorrhage,assessment of injury and outcomes,and even as a biomarker of therapeutic targets.
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Construction of artificial cell factory to produce specific compounds of interest needs wild strain to be genetically engineered. In recent years, with the reconstruction of many genome-scale metabolic networks, a number of methods have been proposed based on metabolic network analysis for predicting genetic modification targets that lead to overproduction of compounds of interest. These approaches use constraints of stoichiometry and reaction reversibility in genome-scale models of metabolism and adopt different mathematical algorithms to predict modification targets, and thus can discover new targets that are difficult to find through traditional intuitive methods. In this review, we introduce the principle, merit, demerit and application of various strain optimization methods in detail. The main problems in existing methods and perspectives on this emerging research field are also discussed, aiming to provide guidance to choose the appropriate methods according to different types of products and the reliability of the predicted results.
Subject(s)
Algorithms , Biotechnology , Methods , Computer Simulation , Genome , Industrial Microbiology , Metabolic Engineering , Methods , Metabolic Networks and Pathways , Models, Theoretical , Reproducibility of ResultsABSTRACT
Cerebral salt wasting syndrome (CSWS) is a common cause of refractory hyponatremia. Early diagnosis and treatment of CSWS can greatly improve the patient′s condition and improve the prognosis. Clinically by supplying sodium hydrate, most patients can resume normal serum sodium level, and get remission. But a few patients with low serum sodium, high urine sodium and low blood volume can not improve and even worse. Fludrocortisone and adrenal cortical hormone can rapidly and effectively reduce the urinary sodium level and urine volume, correct hyponatremia and low blood volume and improve the prognosis in such patients.
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Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
Subject(s)
Humans , ATP-Binding Cassette Transporters , Genetics , DNA-Binding Proteins , Genetics , Homeostasis , Lung Diseases , Genetics , Pulmonary Surfactant-Associated Protein C , Genetics , Pulmonary Surfactants , Metabolism , Transcription FactorsABSTRACT
In the last few years, high-throughput (or 'next-generation') sequencing technologies have delivered a step change in our ability to sequence genomes, whether human or bacterial. Further comparative genome analysis enables us to reveal detailed knowledge of genetics or physiology of industrial important strains obtained in laboratory, to analyze genotype-phenotype correlations of mutants with improved performance. Based on identified key mutations or mutation combinations, Inverse Metabolic Engineering (IME) can be performed by using accurate genetic modification system. Recently, IME has been successfully used for strain improvement and has become a research hotspot, including improving substrate utilization, engineering the robustness of industrial microbes and enhancing production of bio-based products. Here, we describe recent advances in research methods of IME, with an emphasis on characterization of genotype-phenotype and the latest advances and application of IME. Possible directions and challenges for further development of IME are also discussed.
Subject(s)
Industrial Microbiology , Metabolic Engineering , MutationABSTRACT
Lignocellulosic biomass represents an abundant, low-cost and renewable source of potentially fermentable sugars. It is acandidate besides petroleum as feedstock for fuel and chemical production. Recent researches on utilizing lignocellulosicsas feedstock boost development of numerous-promising processes for a variety of fuels and chemicals, such as biodiesel, biohydrogen and ethanol. However, high cost in depolymerization is a primary obstacle preventing the use of lignocellulosic biomass as feedstock. Consolidated bioprocessing (CBP), refers to the bioprocess without any exogenous cellulolyotic enzymes added, converting the lignocellulosic material into biochemicals directly, which could potentially avoid the cost of the dedicated enzyme generation step by incorporating enzyme-generating, biomass-degrading and bioproduct-producing capabilities into a single organism through genetic engineering. There are two CBP strategies, native strategy and recombinant strategy. We mainly introduce the recombinant strategy, including its principle, the two responding styles, the contributions of synthetic biology and metabolic engineering and the future challenges.
Subject(s)
Bacteria , Genetics , Metabolism , Biofuels , Biotechnology , Methods , Ethanol , Metabolism , Fungi , Genetics , Metabolism , Hydrolases , Genetics , Industrial Microbiology , Methods , Lignin , Metabolism , Metabolic Engineering , Methods , Recombinant Proteins , GeneticsABSTRACT
ObjectiveTo explore the function of intraoperative monitoring by brainstem auditory evoked potential and free electromyography during the operation of large acoustic neuroma for improving the operation more accurately and safely. MethodsThe intraoperative monitoring of affected cranial nerve and brainstem function respectively by brainstem auditory evoked potential and free electromyography was performed in 26 patients with large acoustic neuroma. According to the monitoring result the strategy and method of surgery was adjusted. Facial nerve function was assessed using the House-Brackmann facial nerve grading system immediately after two weeks of surgery.Results23 cases (88 ％) achieved total resection,3 cases(12 ％)achieved subtotal resection. The facial nerve was preserved anatomically in 25 patients.According to the House-Brackmann facial nerve grading system,21 cases (80 ％) got preserve of facial nerve function in grade Ⅰ - Ⅱ, 3 cases(12 ％)got preserve of facial nerve function in grade ]Ⅲ-Ⅳ and 1 cases (4 ％) got preserve of facial nerve function in grade Ⅴ after two weeks of surgery.ConclusionIntraoperative physiological monitoring may increase the anatomical and functional preservation rate of affected cranial nerve and also may improve the operation more accurately and safely.
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High-throughput data supply a basis for the reconstruction of genome-scale metabolic networks, and meanwhile bring challenges to the reconstruction and analysis methods. With the increasing of data quantity, the time-consuming manual reconstruction and analysis are far behind the improvement of models. Therefore, various automatic methods emerge. The automatic reconstruction and analysis have irreplaceable effect in the standardization and programming of reconstruction and analysis methods, as well as largely improving the speed of reconstruction and understanding of the metabolic network. In this review, we introduced the progress of automatic reconstruction and the main analysis tools of genome-scale metabolic network. We further summarized the workflow of automatic reconstruction. The difficulties and perspectives on this research field are also discussed.
Subject(s)
Humans , Electronic Data Processing , Genome , Metabolic Networks and Pathways , Models, Theoretical , SoftwareABSTRACT
Omics technologies have profoundly promoted development and applications of metabolic engineering by analysis of cell metabolism at a system level. Whole genome transcription profiles have provided researchers more rigorous evaluation of cell phenotype and an increased understanding of cellular metabolism. Furthermore, transcriptome analysis can conduce to identification of effective gene targets for strain improvement, and consequently accelerates rational design and construction of microbial cell factories for desired product. In this review, we briefly introduced the principle of three main platforms of transcriptome, and reviewed the recent applications of the transcriptome to metabolic engineering, finally provided conclusions and future prospects.
Subject(s)
Biotechnology , Methods , Genomics , Methods , Industrial Microbiology , Methods , Metabolic Engineering , Methods , Metabolic Networks and Pathways , TranscriptomeABSTRACT
Dozens of genome-scale metabolic networks have been reconstructed by integrating information from various databases on genes, proteins, metabolites and validated by experiment data from the literature. The reconstructed networks can be used to quantitatively investigate the interactions between components of a biological system at a system level. Such theoretical study could help us understand the organization principle of the large scale network and thus provide guidance to strain optimization through metabolic engineering technology. In this review, we evaluate the methods for the reconstruction, analysis and application of genome-scale metabolic networks. The difficulties and perspectives on this emerging research field are also discussed.
Subject(s)
Biotechnology , Methods , Genetic Engineering , Genomics , Methods , Industrial Microbiology , Metabolic Networks and Pathways , PhysiologyABSTRACT
Proteomics was important for the coherent study of human reproduction and animal breeding including human infertility,sperm-egg binding and mutual recognition of the mechanism.It was well known that proteomics had become one of the main branches of life sciences in the future.This provides the technological means and theoretical foundation for the individual dynamic changes in the protein.At the same time,it plays an important role in the drug development,the mechanism of life activities and in the field of livestock breeding.
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The enantiomeric resolution of lactic acid was studied by reversed high performance liquid chromatography. β-cyclodextrin (β-CD), dimethyl (DM) and TM-β-CD were used as chiral mobile phase additives. The effects of different mobile phase, pH and concentration of chiral mobile phase additives on resolution of D,L-lactic acid were investigated. The results showed: the enantioselectivity of TM-β-CD was better than those of β-CD and DM-β-CD. D,L-lactic acid could be partly separated by DM-β-CD and could not be separated by β-CD, while it could be fully separated by TM-β-CD. As the concentration of TM-β-CD changed from 0.20 mmol/L to 1.00 mmol/L, The resolution varied slightly. The experiment of the effect of pH of mobile phase on Rs showed: as pH changed from 2.4 to 3.0, the Rs remain stable, and when pH＞3.1, the Rs decreased with the increase of pH. The RSD of retention time of L-lactic acid and D-lactic acid were 0.2% and 0.2%, respectively. The chromatographic systems with a dynamically-generated stationary phase with 2,3,6-tri-O-methyl-β-cyclodextrin proved to be an effective method for lactic acid enantiomer separation
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Object To study the separation effect of three macoroporous resins for lycopene and ? carotene, in order to optimize the suitable one. Methods The performances of adsorption and desorption for lycopene and ? carotene with three macroporous resins D4020, X 5 and AB 8 were compared, and adsorption dynamics process of resins was studied. Results The adsorptive capacities of X 5 resin for lycopene and ? carotene are the most, they are 7 44 and 11 2 mg/g, respectively. Desorption ratio of X 5 resin is the highest. Conclusion X 5 resin is an ideal adsorbent for lycopene and ? carotene extraction.