The static approach of representing metabolic pathway diagrams offers no flexibility. Thus, many systems adopt automatic graph layout techniques to visualize the topological architecture of pathways. There are weaknesses, however, because automatically drawn figures are generally difficult to understand. The problem becomes even more serious when we attempt to visualize all of the information in a single, big picture, which usually results in a confusing diagram. To provide a partial solution to this thorny issue, we propose J2dpathway, a metabolic pathway atlas viewer that has node-abstracting features.
Metabolic Networks and Pathways ; Pliability

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.
Genome ; Metabolic Networks and Pathways

For the direct understanding of flow, pathway data are usually represented as directed graphs in biological journals and texts. Databases of metabolic pathways or signal transduction pathways inevitably contain these kinds of graphs to show the flow. KEGG, one of the representative pathway databases, uses the manually drawn figure which can not be easily maintained. Graph layout algorithms are applied for visualizing metabolic pathways in some databases, such as EcoCyc. Although these can express any changes of data in the real time, it exponentially increases the edge crossings according to the increase of nodes. For the understanding of genome scale flow of metabolism, it is very important to reduce the unnecessary edge crossings which exist in the automatic graph layout. We propose a metabolic pathway drawing algorithm for reducing the number of edge crossings by considering the fact that metabolic pathway graph is scale-free network. The experimental results show that the number of edge crossings is reduced about 37~40% by the consideration of scale-free network in contrast with non-considering scale-free network. And also we found that the increase of nodes do not always mean that there is an increase of edge crossings.
Genome ; Metabolic Networks and Pathways* ; Metabolism ; Signal Transduction

The characteristics of metabolic pathways make them particularly amenable to layered graph drawing methods. This paper presents a visual Java-based tool for drawing and annotating biological pathways in twoand- a-half dimensions (2.5D) as an alternative to three dimensional (3D) visualizations. Such visualization allows user to display different groups of clustered nodes, in different parallel planes, and to see a detailed view of a group of objects in focus and its place in the context of the whole system. This tool is an extended version of J2dPathway.
Hypogonadism ; Metabolic Networks and Pathways ; Mitochondrial Diseases ; Ophthalmoplegia

The basic graph layout technique, one of many visualization techniques, deals with the problem of positioning vertices in a way to maximize some measure of desirability in a graph. The technique is becoming critically important for further development of the field of systems biology. However, applying the appropriate automatic graph layout techniques to the genomic scale flow of metabolism requires an understanding of the characteristics and patterns of duplicate and shared vertices, which is crucial for bioinformatics software developers. In this paper, we provide the results of parsing KEGG XML files from a graph-theoretical perspective, for future research in the area of automatic layout techniques in biological pathway domains.
Computational Biology ; Metabolic Networks and Pathways ; Systems Biology

Metabolomics is an emerging and popular subject in the post-genome era, and a large number of studies have been noted on the application of metabolomics in health evaluation, growth and development evaluation, disease diagnosis, and therapeutic efficacy evaluation. As a special period of life, the neonatal period is characterized by rapid cell renewing, consumption of a lot of energy and materials, and changes in metabolic pathways, all of which affect the level of metabolites. However, there is still no reference standard for metabolic level and profile in neonates. This article reviews the current status of metabolic research on neonatal growth and development and common diseases and related clinical application of metabolomics, so as to provide new ideas for nutrition guidance and evaluation, selection of therapeutic regimens, and new drug research in neonates.
Humans ; Infant, Newborn ; Metabolic Networks and Pathways ; Metabolomics

Metabolic engineering is a powerful tool to increase many valuable metabolites through enhancing pathways or introducing exogenous pathways from other organisms. As the complexity of the targeted structure increases, many problems arise when the host suffers from flux imbalance and some toxic effects. An emerging approach to solve these problems is the use of synthetic scaffolds to co-localize key enzymes and metabolites of the synthetic pathways, enhance the metabolic flux and limit the interaction between intermediate products in the host cell. Although many scaffolds made of proteins and nucleic acids have been explored and applied to a variety of research to the heterogeneous synthesis of multiple metabolites, success is rather limited. The precise assembly of synthetic scaffolds remains a difficult task. In this review, we summarized the application of synthetic scaffolds in metabolic engineering, and outlined the main principle of scaffold designs, then highlighted the current challenges in their application.
Metabolic Engineering ; Metabolic Networks and Pathways ; Proteins ; Synthetic Biology

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.
Genome ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Models, Biological ; Thermodynamics

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.
Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Synthetic Biology

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 aroG^fbr. 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.
Escherichia coli/metabolism* ; Tryptophan ; Metabolic Engineering ; Bioreactors ; Metabolic Networks and Pathways