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1.
Chinese Journal of Biotechnology ; (12): 4663-4681, 2023.
Article in Chinese | WPRIM | ID: wpr-1008049

ABSTRACT

The present study aimed to unravel the carbon metabolism pathway of Acinetobacter sp. TAC-1, a heterotrophic nitrification-aerobic denitrification (HN-AD) strain that utilizes poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as a carbon source. Sodium acetate was employed as a control to assess the gene expression of carbon metabolic pathways in the TAC-1 strain. The results of genome sequencing demonstrated that the TAC-1 strain possessed various genes encoding carbon metabolic enzymes, such as gltA, icd, sucAB, acs, and pckA. KEGG pathway database analysis further verified the presence of carbon metabolism pathways, including the glycolytic pathway (EMP), pentose phosphate pathway (PPP), glyoxylate cycle (GAC), and tricarboxylic acid (TCA) cycle in the TAC-1 strain. The differential expression of metabolites derived from distinct carbon sources provided further evidence that the carbon metabolism pathway of TAC-1 utilizing PHBV follows the sequential process of PHBV (via the PPP pathway)→gluconate (via the EMP pathway)→acetyl-CoA (entering the TCA cycle)→CO2+H2O (generating electron donors and releasing energy). This study is expected to furnish a theoretical foundation for the advancement and implementation of novel denitrification processes based on HN-AD and solid carbon sources.


Subject(s)
3-Hydroxybutyric Acid , Carbon/metabolism , Polyesters , Hydroxybutyrates , Metabolic Networks and Pathways
2.
Chinese Journal of Biotechnology ; (12): 4550-4562, 2023.
Article in Chinese | WPRIM | ID: wpr-1008041

ABSTRACT

Mycobacterium neoaurum has the ability to produce steroidal intermediates known as 22-hydroxy-23, 24-bisnorchol-4-en-3-one (BA) upon the knockout of the genes for either the hydroxyacyl-CoA dehydrogenase (Hsd4A) or acyl-CoA thiolase (FadA5). In a previous study, we discovered a novel metabolite in the fermentation products when the fadA5 gene was deleted. This research aims to elucidate the metabolic pathway of this metabolite through structural identification, homologous sequence analysis of the fadA5 gene, phylogenetic tree analysis of M. neoaurum HGMS2, and gene knockout. Our findings revealed that the metabolite is a C23 metabolic intermediate, named 24-norchol-4-ene-3, 22-dione (designated as 3-OPD). It is formed when a thioesterase (TE) catalyzes the formation of a β-ketonic acid by removing CoA from the side chain of 3, 22-dioxo-25, 26-bisnorchol-4-ene-24-oyl CoA (22-O-BNC-CoA), followed by spontaneously undergoing decarboxylation. These results have the potential to contribute to the development of novel steroid intermediates.


Subject(s)
Mycobacterium/metabolism , Phylogeny , Steroids/metabolism , Metabolic Networks and Pathways , Sterols/metabolism
3.
Chinese Journal of Biotechnology ; (12): 3566-3578, 2023.
Article in Chinese | WPRIM | ID: wpr-1007977

ABSTRACT

As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses use the energy and precursors provided by the metabolic network of the host cells to drive their replication, assembly and release. Namely, viruses hijack the host cells metabolism to achieve their own replication and proliferation. In addition, viruses can also affect host cell metabolism by the expression of auxiliary metabolic genes (AMGs), affecting carbon, nitrogen, phosphorus, and sulfur cycles, and participate in microbial-driven biogeochemical cycling. This review summarizes the effect of viral infection on the host's core metabolic pathway from four aspects: cellular glucose metabolism, glutamine metabolism, fatty acid metabolism, and viral AMGs on host metabolism. It may facilitate in-depth understanding of virus-host interactions, and provide a theoretical basis for the treatment of viral diseases through metabolic intervention.


Subject(s)
Humans , Metabolic Networks and Pathways , Virus Diseases , Carbohydrate Metabolism , Host Microbial Interactions , Lipid Metabolism
4.
Chinese Journal of Biotechnology ; (12): 3015-3036, 2023.
Article in Chinese | WPRIM | ID: wpr-981246

ABSTRACT

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.


Subject(s)
Flavonoids/metabolism , Fruit/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Lycium/metabolism , Metabolic Networks and Pathways , Transcriptome
5.
Chinese Journal of Biotechnology ; (12): 2430-2448, 2023.
Article in Chinese | WPRIM | ID: wpr-981210

ABSTRACT

Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.


Subject(s)
Humans , Methanol/metabolism , Metabolic Engineering , Metabolic Networks and Pathways , Biotransformation
6.
Chinese Journal of Biotechnology ; (12): 2359-2374, 2023.
Article in Chinese | WPRIM | ID: wpr-981206

ABSTRACT

As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroGfbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.


Subject(s)
Escherichia coli/metabolism , Tryptophan , Metabolic Engineering , Bioreactors , Metabolic Networks and Pathways
7.
Journal of Zhejiang University. Science. B ; (12): 157-171, 2023.
Article in English | WPRIM | ID: wpr-971477

ABSTRACT

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lyciumbarbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl4). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl4 solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl4-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.


Subject(s)
Animals , Dogs , Antioxidants/metabolism , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury/drug therapy , Kelch-Like ECH-Associated Protein 1/metabolism , Liver , Metabolic Networks and Pathways , Mitochondria/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Polysaccharides/pharmacology , Lycium/chemistry
8.
Neuroscience Bulletin ; (6): 1087-1104, 2023.
Article in English | WPRIM | ID: wpr-982458

ABSTRACT

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.


Subject(s)
Mice , Animals , Memory , Chromatin Assembly and Disassembly , Hippocampus/metabolism , Transcription Factors/metabolism , Chromatin/metabolism , Metabolic Networks and Pathways
9.
Chinese Journal of Oncology ; (12): 1369-1375, 2022.
Article in Chinese | WPRIM | ID: wpr-969797

ABSTRACT

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.


Subject(s)
Male , Female , Humans , Middle Aged , Adult , Aged , Cysteine , Multiple Myeloma/diagnosis , Reproducibility of Results , Metabolome , Metabolomics/methods , Metabolic Networks and Pathways , Methionine , Serine , Phenylalanine , Threonine , Biomarkers
10.
Chinese Journal of Biotechnology ; (12): 4765-4778, 2022.
Article in Chinese | WPRIM | ID: wpr-970347

ABSTRACT

Anaerobic digestion is another important anaerobic catabolism pathway besides lactic acid and ethanol fermentation, which is of great significance for recycling resources, maintaining the ecological balance, optimizing the energy structure, alleviating the energy crisis, and promoting the implementation of the "Carbon Peaking and Carbon Neutrality" strategy. However, such an important metabolic process has not been involved in the current textbooks and teaching of biochemistry courses, making the teaching system incomplete. The anaerobic digestion process involves many reactions and complex metabolic pathways. In order to improve the students' understanding to this process, we created a full chart of the whole anaerobic digestion process based on systemic literature review and integrated it into the classroom teaching through the BOPPPS teaching mode. It was found that the classroom teaching assisted by this metabolic chart could help students establish the structural framework of the anaerobic digestion process and enrich the knowledge system of metabolism, achieving a good teaching effect. This paper introduces the content of the metabolic pathways of anaerobic digestion and the design of the teaching process, which would facilitate the teaching reforms and perfection of textbooks for related courses, such as Biochemistry, Environmental Engineering Microbiology and New Energy Engineering.


Subject(s)
Humans , Anaerobiosis , Biochemistry/education , Students , Metabolic Networks and Pathways , Fermentation
11.
Chinese Journal of Biotechnology ; (12): 4462-4497, 2022.
Article in Chinese | WPRIM | ID: wpr-970327

ABSTRACT

Neonicotinoid compounds are usually considered harmless and eco-friendly in terms of their targeted toxicity compared to that of pyrethroids and phosphorus-containing pesticides. However, overuse of neonicotinoid insecticides resulted in the accumulation of its residuals or intermediates in soil and water, which consequently affected beneficial insects as well as mammals, yielding pollution and secondary risks. This review summarized the recent advances in neonicotinoid degrading microorganisms and their metabolic diversity, with the aim to address the urgent need for degrading these insecticides. These advances may facilitate the development of controllable and reliable technologies for efficiently transforming neonicotinoid insecticides into value-added products by synthetic biology and metagenomics.


Subject(s)
Animals , Neonicotinoids/metabolism , Insecticides/metabolism , Soil , Environmental Pollution , Metabolic Networks and Pathways , Mammals/metabolism
12.
Chinese Journal of Biotechnology ; (12): 1554-1564, 2022.
Article in Chinese | WPRIM | ID: wpr-927800

ABSTRACT

Graph-theory-based pathway analysis is a commonly used method for pathway searching in genome-scale metabolic networks. However, such searching often results in many pathways biologically infeasible due to the presence of currency metabolites (e.g. H+, H2O, CO2, ATP etc.). Several methods have been proposed to address the problem but up to now there is no well-recognized methods for processing the currency metabolites. In this study, we proposed a new method based on the function of currency metabolites for transferring of functional groups such as phosphate. We processed most currency metabolites as pairs rather than individual metabolites, and ranked the pairs based on their importance in transferring functional groups, in order to make sure at least one main metabolite link exists for any reaction. The whole process can be done automatically by programming. Comparison with existing approaches indicates that more biologically infeasible pathways were removed by our method and the calculated pathways were more reliable, which may facilitate the graph-theory-based pathway design and visualization.


Subject(s)
Genome , Metabolic Networks and Pathways
13.
Chinese Journal of Biotechnology ; (12): 1390-1407, 2022.
Article in Chinese | WPRIM | ID: wpr-927788

ABSTRACT

It is among the goals in metabolic engineering to construct microbial cell factories producing high-yield and high value-added target products, and an important solution is to design efficient synthetic pathway for the target products. However, due to the difference in metabolic capacity among microbial chassises, the available substrate and the yielded products are limited. Therefore, it is urgent to design related metabolic pathways to improve the production capacity. Existing metabolic engineering approaches to designing heterologous pathways are mainly based on biological experience, which are inefficient. Moreover, the yielded results are in no way comprehensive. However, systems biology provides new methods for heterologous pathway design, particularly the graph-based and constraint-based methods. Based on the databases containing rich metabolism information, they search for and uncover possible metabolic pathways with designated strategy (graph-based method) or algorithm (constraint-based method) and then screen out the optimal pathway to guide the modification of strains. In this paper, we reviewed the databases and algorithms for pathway design, and the applications in metabolic engineering and discussed the strengths and weaknesses of existing algorithms in practical application, hoping to provide a reference for the selection of optimal methods for the design of product synthesis pathway.


Subject(s)
Algorithms , Biosynthetic Pathways , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Systems Biology
14.
Chinese Journal of Biotechnology ; (12): 531-545, 2022.
Article in Chinese | WPRIM | ID: wpr-927726

ABSTRACT

Constraint-based genome-scale metabolic network models (genome-scale metabolic models, GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric constraints, other constraints such as enzyme availability and thermodynamic feasibility may also limit the cellular phenotype solution space. Recently, extended GEM models considering either enzymatic or thermodynamic constraints have been developed to improve model prediction accuracy. This review summarizes the recent progresses on metabolic models with multiple constraints (MCGEMs). We presented the construction methods and various applications of MCGEMs including the simulation of gene knockout, prediction of biologically feasible pathways and identification of bottleneck steps. By integrating multiple constraints in a consistent modeling framework, MCGEMs can predict the metabolic bottlenecks and key controlling and modification targets for pathway optimization more precisely, and thus may provide more reliable design results to guide metabolic engineering of industrially important microorganisms.


Subject(s)
Genome , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Models, Biological , Thermodynamics
15.
Chinese Journal of Biotechnology ; (12): 2211-2222, 2021.
Article in Chinese | WPRIM | ID: wpr-887790

ABSTRACT

Synthetic biology and metabolic engineering have been widely used to construct microbial cell factories for efficient production of bio-based chemicals, which mainly focus on the modification and regulation of metabolic pathways. The characteristics of microorganisms themselves, e.g. morphology, have rarely been taken into consideration in the biotechnological production processes. Morphology engineering aims to control cell shapes and cell division patterns by manipulating the genes related to cell morphology, providing a new strategy for developing efficient microbial cell factories. This review summarized the proteins related to cell morphology, followed by illustrating a few examples of using morphology engineering strategies for improving production of bio-based chemicals. This includes increasing intracellular product accumulation by regulating cell size, enhancing extracellular secretion of target products by improving cell permeability, reducing production cost by achieving high cell density, and improving product performance by controlling the degree of product hydrolysis. Finally, challenges and perspectives for the development of morphology engineering were discussed.


Subject(s)
Biotechnology , Metabolic Engineering , Metabolic Networks and Pathways , Synthetic Biology
16.
Frontiers of Medicine ; (4): 383-403, 2021.
Article in English | WPRIM | ID: wpr-888735

ABSTRACT

Cancer development is a complicated process controlled by the interplay of multiple signaling pathways and restrained by oxygen and nutrient accessibility in the tumor microenvironment. High plasticity in using diverse nutrients to adapt to metabolic stress is one of the hallmarks of cancer cells. To respond to nutrient stress and to meet the requirements for rapid cell proliferation, cancer cells reprogram metabolic pathways to take up more glucose and coordinate the production of energy and intermediates for biosynthesis. Such actions involve gene expression and activity regulation by the moonlighting function of oncoproteins and metabolic enzymes. The signal - moonlighting protein - metabolism axis facilitates the adaptation of tumor cells under varying environment conditions and can be therapeutically targeted for cancer treatment.


Subject(s)
Humans , Energy Metabolism , Epigenesis, Genetic , Metabolic Networks and Pathways , Neoplasms/genetics , Tumor Microenvironment
17.
Chinese Journal of Biotechnology ; (12): 1564-1577, 2021.
Article in Chinese | WPRIM | ID: wpr-878655

ABSTRACT

As an important model industrial microorganism, Escherichia coli has been widely used in pharmaceutical, chemical industry and agriculture. In the past 30 years, a variety of new strategies and techniques, including artificial intelligence, gene editing, metabolic pathway assembly, and dynamic regulation have been used to design, construct, and optimize E. coli cell factories, which remarkably improved the efficiency for biotechnological production of chemicals. In this review, three key aspects for constructing E. coli cell factories, including pathway design, pathway assembly and regulation, and optimization of global cellular performance, are summarized. The technologies that have played important roles in metabolic engineering of E. coli, as well as their future applications, are discussed.


Subject(s)
Artificial Intelligence , Escherichia coli/genetics , Gene Editing , Metabolic Engineering , Metabolic Networks and Pathways/genetics
18.
Chinese Journal of Biotechnology ; (12): 1541-1563, 2021.
Article in Chinese | WPRIM | ID: wpr-878654

ABSTRACT

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.


Subject(s)
Metabolic Engineering , Metabolic Networks and Pathways/genetics , Synthetic Biology
19.
Chinese Journal of Biotechnology ; (12): 1526-1540, 2021.
Article in Chinese | WPRIM | ID: wpr-878653

ABSTRACT

Genome-scale metabolic network model (GSMM) is becoming an important tool for studying cellular metabolic characteristics, and remarkable advances in relevant theories and methods have been made. Recently, various constraint-based GSMMs that integrated genomic, transcriptomic, proteomic, and thermodynamic data have been developed. These developments, together with the theoretical breakthroughs, have greatly contributed to identification of target genes, systems metabolic engineering, drug discovery, understanding disease mechanism, and many others. This review summarizes how to incorporate transcriptomic, proteomic, and thermodynamic-constraints into GSMM, and illustrates the shortcomings and challenges of applying each of these methods. Finally, we illustrate how to develop and refine a fully integrated GSMM by incorporating transcriptomic, proteomic, and thermodynamic constraints, and discuss future perspectives of constraint-based GSMM.


Subject(s)
Genome/genetics , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Models, Biological , Proteomics
20.
Chinese Journal of Biotechnology ; (12): 1494-1509, 2021.
Article in Chinese | WPRIM | ID: wpr-878651

ABSTRACT

In 1990s, Bailey and Stephanopoulos put forward the concept of classic metabolic engineering, aiming to use DNA recombination technology to rewire metabolic network to achieve improved cell performance and increased target products. In the last 30 years since the birth of metabolic engineering, life science have flourished, and new disciplines such as genomics, systems biology and synthetic biology have emerged, injecting new connotations and vitality into the development of metabolic engineering. Classic metabolic engineering research has entered into an unprecedented stage of systems metabolic engineering. The application of synthetic biology tools and strategies, such as omics technology, genomic-scale metabolic model, parts assembly, circuits design, dynamic control, genome editing and many others, have greatly improved the design, build, and rewiring capabilities of complex metabolism. The intervention of machine learning and the combination of evolutionary engineering and metabolic engineering will further promote the development of systems metabolic engineering. This paper analyzes the development of metabolic engineering in the past 30 years and summarizes the novel theories, techniques, strategies, and applications of metabolic engineering that have emerged over the past 30 years.


Subject(s)
Gene Editing , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Synthetic Biology , Systems Biology
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