Search

The screening of enzymes for catalyzing specific substrate–product pairs is often constrained in the realms of metabolic engineering and synthetic biology. Existing tools based on substrate and reaction similarity predominantly rely on prior knowledge, demonstrating limited extrapolative capabilities and an inability to incorporate custom candidate-enzyme libraries. Addressing these limitations, we have developed the Substrate–product Pair-based Enzyme Promiscuity Prediction (SPEPP) model. This innovative approach utilizes transfer learning and transformer architecture to predict enzyme promiscuity, thereby elucidating the intricate interplay between enzymes and substrate–product pairs. SPEPP exhibited robust predictive ability, eliminating the need for prior knowledge of reactions and allowing users to define their own candidate-enzyme libraries. It can be seamlessly integrated into various applications, including metabolic engineering, de novo pathway design, and hazardous material degradation. To better assist metabolic engineers in designing and refining biochemical pathways, particularly those without programming skills, we also designed EnzyPick, an easy-to-use web server for enzyme screening based on SPEPP. EnzyPick is accessible at http://www.biosynther.com/enzypick/. [ABSTRACT FROM AUTHOR]

Motivation Despite low prevalence, rare diseases affect 300 million people worldwide. Research on pathogenesis and drug development lags due to limited commercial potential, insufficient epidemiological data, and a dearth of publications. The unique characteristics of rare diseases, including limited annotated data, intricate processes for extracting pertinent entity relationships, and difficulties in standardizing data, represent challenges for text mining. Results We developed a rare disease data acquisition framework using text mining and knowledge graphs and constructed the most comprehensive rare disease knowledge graph to date, Rare Disease Bridge (RDBridge). RDBridge offers search functions for genes, potential drugs, pathways, literature, and medical imaging data that will support mechanistic research, drug development, diagnosis, and treatment for rare diseases. Availability and implementation RDBridge is freely available at http://rdb.lifesynther.com/. [ABSTRACT FROM AUTHOR]

Summary Cosmetics form an important part of our daily lives, and it is therefore important to understand the basic physicochemical properties, metabolic pathways, and toxicological and safe concentrations of these cosmetics molecules. Therefore, comprehensive cosmetic ingredients bioinformatics platform (CCIBP) was developed here, which is a unique comprehensive cosmetic database providing information on regulations, physicochemical properties, and human metabolic pathways for cosmetic molecules from major regions of the world, whilst also correlating plant information in natural products. CCIBP supports formulation analysis, efficacy component analysis, and also combines knowledge of synthetic biology to facilitate access to natural molecules and biosynthetic production. CCIBP, empowered with chemoinformatics, bioinformatics, and synthetic biology data and tools, presents a very helpful platform for cosmetic research and development of ingredients. Availability and implementation CCIBP is available at: http://design.rxnfinder.org/cosing/ [ABSTRACT FROM AUTHOR]

Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications. Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) play a crucial role in modulating the inflammatory response and participated in sepsis-related immune dysfunctions. However, little is known about the regulatory mechanisms by which Tregs are kept in check during immune responses. Here, we verified the simultaneous expression of interleukin-3 (IL-3) and its receptor (IL-3R) in Tregs. Then, by modulation of IL-3 expression via lentiviral transduction-mediated small interfering RNA, we demonstrated that IL-3 negatively regulated Tregs activity via an autocrine mechanism. Furthermore, we found that anti-IL-3 antibody treatment significantly diminished inflammatory cytokines and organ injury, and improved survival in septic mice, which was associated with enhanced Treg percentage and function. Collectively, these results suggest that IL-3 negatively regulates the activity of Tregs in a previously unrecognized autocrine manner, and plays an important role in the excessive inflammatory response in sepsis, which might be utilized as a therapeutic strategy for the treatment of complications in sepsis. [ABSTRACT FROM AUTHOR]

A proliferation of chemical, reaction and enzyme databases, new computational methods and software tools for data-driven rational biosynthesis design have emerged in recent years. With the coming of the era of big data, particularly in the bio-medical field, data-driven rational biosynthesis design could potentially be useful to construct target-oriented chassis organisms. Engineering the complicated metabolic systems of chassis organisms to biosynthesize target molecules from inexpensive biomass is the main goal of cell factory design. The process of data-driven cell factory design could be divided into several parts: (1) target molecule selection; (2) metabolic reaction and pathway design; (3) prediction of novel enzymes based on protein domain and structure transformation of biosynthetic reactions; (4) construction of large-scale DNA for metabolic pathways; and (5) DNA assembly methods and visualization tools. The construction of a one-stop cell factory system could achieve automated design from the molecule level to the chassis level. In this article, we outline data-driven rational biosynthesis design steps and provide an overview of related tools in individual steps. [ABSTRACT FROM AUTHOR]

Background and Aims Differences in local abundance and ploidy level are predicted to impact the direction of introgression between species. Here, we tested these hypotheses on populations of Betula albosinensis (red birch) and Betula platyphylla (white birch) which were thought to differ in ploidy level, the former being tetraploid and the latter diploid. Methods We sampled 391 birch individuals from nine localities in China, and classified them into species based on leaf morphology. Twelve nuclear microsatellite markers were genotyped in each sample, and analysed using principal coordinates analysis and STRUCTURE software. We compared the effects of two different methods of scoring polyploid genotypes on population genetic analyses. We analysed the effect of ploidy, local species abundance and latitude on levels of introgression between the species. Key Results Leaf morphology divided our samples into red and white birch, but genetic analyses unexpectedly revealed two groups within red birch, one of which was tetraploid, as expected, but the other of which appeared to have diploid microsatellite genotypes. Five individuals were identified as early-generation hybrids or backcrosses between white birch and red birch and five were identified between red birch and 'diploid' red birch. Cline analysis showed that levels of admixture were not significantly correlated with latitude. Estimated genetic differentiation among species was not significantly different between determined tetraploid and undetermined tetraploid genotypes. Conclusions Limited hybridization and gene flow have occurred between red birch and white birch. Relative species abundance and ploidy level do not impact the direction of introgression between them, as genetic admixture is roughly symmetrical. We unexpectedly found populations of apparently diploid red birch and this taxon may be a progenitor of allotetraploid red birch populations. Incomplete lineage sorting may explain patterns of genetic admixture between apparently diploid and allotetraploid red birch. [ABSTRACT FROM AUTHOR]

Summary Advances in metabolic engineering have boosted the production of bulk chemicals, resulting in tons of production volumes of some bulk chemicals with very low prices. A decrease in the production cost and overproduction of bulk chemicals makes it necessary and desirable to explore the potential to synthesize higher-value products from them. It is also useful and important for society to explore the use of design methods involving synthetic biology to increase the economic value of these bulk chemicals. Therefore, we developed 'BioBulkFoundary', which provides an elaborate analysis of the biosynthetic potential of bulk chemicals based on the state-of-art exploration of pathways to synthesize value-added chemicals, along with associated comprehensive technology and economic database into a user-friendly framework. Availability and implementation Freely available on the web at http://design.rxnfinder.org/biobulkfoundary/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary The field of synthetic biology lacks a comprehensive knowledgebase for selecting synthetic target molecules according to their functions, economic applications and known biosynthetic pathways. We implemented ChemHub, a knowledgebase containing >90 000 chemicals and their functions, along with related biosynthesis information for these chemicals that was manually extracted from >600 000 published studies by more than 100 people over the past 10 years. Availability and implementation Multiple algorithms were implemented to enable biosynthetic pathway design and precursor discovery, which can support investigation of the biosynthetic potential of these functional chemicals. ChemHub is freely available at: http://www.rxnfinder.org/chemhub/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation The 2019 novel coronavirus outbreak has significantly affected global health and society. Thus, predicting biological function from pathogen sequence is crucial and urgently needed. However, little work has been conducted to identify viruses by the enzymes that they encode, and which are key to pathogen propagation. Results We built a comprehensive scientific resource, SARS2020, which integrates coronavirus-related research, genomic sequences and results of anti-viral drug trials. In addition, we built a consensus sequence-catalytic function model from which we identified the novel coronavirus as encoding the same proteinase as the severe acute respiratory syndrome virus. This data-driven sequence-based strategy will enable rapid identification of agents responsible for future epidemics. Availabilityand implementation SARS2020 is available at http://design.rxnfinder.org/sars2020/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Rapid advances in sequencing technology have resulted huge increases in the accessibility of sequencing data. Moreover, researchers are focusing more on organisms that lack a reference genome. However, few easy-to-use web servers focusing on annotations of enzymatic functions are available. Accordingly, in this study, we describe Transcriptor, a novel platform for annotating transcripts encoding enzymes. Results The transcripts were evaluated using more than 300 000 in-house enzymatic reactions through bridges of Enzyme Commission numbers. Transcriptor also enabled ontology term identification and along with associated enzymes, visualization and prediction of domains and annotation of regulatory structure, such as long noncoding RNAs, which could facilitate the discovery of new functions in model or nonmodel species. Transcriptor may have applications in elucidation of the roles of organs transcriptomes and secondary metabolite biosynthesis in organisms lacking a reference genome. Availability and implementation Transcriptor is available at http://design.rxnfinder.org/transcriptor/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary Living cell strains have important applications in synthesizing their native compounds and potential for use in studies exploring the universal chemical space. Here, we present a web server named as Cell2Chem which accelerates the search for explored compounds in organisms, facilitating investigations of biosynthesis in unexplored chemical spaces. Cell2Chem uses co-occurrence networks and natural language processing to provide a systematic method for linking living organisms to biosynthesized compounds and the processes that produce these compounds. The Cell2Chem platform comprises 40 370 species and 125 212 compounds. Using reaction pathway and enzyme function in silico prediction methods, Cell2Chem reveals possible biosynthetic pathways of compounds and catalytic functions of proteins to expand unexplored biosynthetic chemical spaces. Cell2Chem can help improve biosynthesis research and enhance the efficiency of synthetic biology. Availability and implementation Cell2Chem is available at: http://www.rxnfinder.org/cell2chem/. [ABSTRACT FROM AUTHOR]

Summary The development of sequencing technologies has generated large amounts of protein sequence data. The automated prediction of the enzymatic reactions of uncharacterized proteins is a major challenge in the field of bioinformatics. Here, we present Bio2Rxn as a web-based tool to provide putative enzymatic reaction predictions for uncharacterized protein sequences. Bio2Rxn adopts a consensus strategy by incorporating six types of enzyme prediction tools. It allows for the efficient integration of these computational resources to maximize the accuracy and comprehensiveness of enzymatic reaction predictions, which facilitates the characterization of the functional roles of target proteins in metabolism. Bio2Rxn further links the enzyme function prediction with more than 300 000 enzymatic reactions, which were manually curated by more than 100 people over the past 9 years from more than 580 000 publications. Availability and implementation Bio2Rxn is available at: http://design.rxnfinder.org/bio2rxn/. Contact qnhu@sibs.ac.cn Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Molecular scaffolds are useful in medicinal chemistry to describe, discuss and visualize series of chemical compounds, biochemical transformations and associated biological properties. Results Here, we present RxnBLAST as a web-based tool for analyzing scaffold transformations and reactive chemical environment features in bioreactions. RxnBLAST extracts chemical features from bioreactions including atom–atom mapping, reaction centers, rules and functional groups to help understand chemical compositions and reaction patterns. Core-to-Core is proposed, which can be utilized in scaffold networks and for constructing a reaction space, as well as providing guidance for subsequent biosynthesis efforts. Availability and implementation RxnBLAST is available at: http://design.rxnfinder.org/rxnblast/. [ABSTRACT FROM AUTHOR]

Summary The biosynthetic ability of living organisms has important applications in producing bulk chemicals, biofuels and natural products. Based on the most comprehensive biosynthesis knowledgebase, a computational system, BCSExplorer, is proposed to discover the unexplored chemical space using nature's biosynthetic potential. BCSExplorer first integrates the most comprehensive biosynthetic reaction database with 280 000 biochemical reactions and 60 000 chemicals biosynthesized globally over the past 130 years. Second, in this study, a biosynthesis tree is computed for a starting chemical molecule based on a comprehensive biotransformation rule library covering almost all biosynthetic possibilities, in which redundant rules are removed using a new algorithm. Moreover, biosynthesis feasibility, drug-likeness and toxicity analysis of a new generation of compounds will be pursued in further studies to meet various needs. BCSExplorer represents a novel method to explore biosynthetically available chemical space. Availability and implementation BCSExplorer is available at: http://www.rxnfinder.org/bcsexplorer/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary Synthetic biology has a great potential to produce high value pharmaceuticals, commodities or bulk chemicals. However, many biosynthetic target molecules have no defined or predicted biosynthetic pathways. Biosynthetic precursors are crucial to create biosynthetic pathways. Thus computer-assisted tools for precursor identification are urgently needed to develop novel metabolic pathways. To this end, we present PrecursorFinder, a computational tool that explores biosynthetic precursors for the query target molecules using chemical structure, similarity as well as MCS (maximum common substructure). This platform comprises more than 60 000 compounds biosynthesized for being promising precursors, which are extracted from >500 000 scientific literatures and manually curated by more than 100 people over the past 8 years. The PrecursorFinder could speed up the process of biosynthesis research and make synthetic biology or metabolic engineering more efficient. Availability and implementation PrecursorFinder is available at: http://www.rxnfinder.org/precursorfinder/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation: Molecular representation for small molecules has been routinely used in QSAR/SAR, virtual screening, database search, ranking, drug ADME/T prediction and other drug discovery processes. To facilitate extensive studies of drug molecules, we developed a freely available, open-source python package called chemoinformatics in python (ChemoPy) for calculating the commonly used structural and physicochemical features. It computes 16 drug feature groups composed of 19 descriptors that include 1135 descriptor values. In addition, it provides seven types of molecular fingerprint systems for drug molecules, including topological fingerprints, electro-topological state (E-state) fingerprints, MACCS keys, FP4 keys, atom pairs fingerprints, topological torsion fingerprints and Morgan/circular fingerprints. By applying a semi-empirical quantum chemistry program MOPAC, ChemoPy can also compute a large number of 3D molecular descriptors conveniently.Availability: The python package, ChemoPy, is freely available via http://code.google.com/p/pychem/downloads/list, and it runs on Linux and MS-Windows.Contact: yizeng_liang@263.netSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

Summary: Biochemical reactions play a key role to help sustain life and allow cells to grow. RxnFinder was developed to search biochemical reactions from KEGG reaction database using three search criteria: molecular structures, molecular fragments and reaction similarity. RxnFinder is helpful to get reference reactions for biosynthesis and xenobiotics metabolism.Availability: RxnFinder is freely available via: http://sdd.whu.edu.cn/rxnfinder.Contact: qnhu@whu.edu.cn [ABSTRACT FROM AUTHOR]