ChemHub: a knowledgebase of functional chemicals for synthetic biology studies.

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.

SARS2020: an integrated platform for identification of novel coronavirus by a consensus sequence-function model.

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.

novoPathFinder: a webserver of designing novel-pathway with integrating GEM-model.

To increase the number of value-added chemicals that can be produced by metabolic engineering and synthetic biology, constructing metabolic space with novel reactions/pathways is crucial. However, with the large number of reactions that existed in the metabolic space and complicated metabolisms within hosts, identifying novel pathways linking two molecules or heterologous pathways when engineering a host to produce a target molecule is an arduous task. Hence, we built a user-friendly web server, novoPathFinder, which has several features: (i) enumerate novel pathways between two specified molecules without considering hosts; (ii) construct heterologous pathways with known or putative reactions for producing target molecule within Escherichia coli or yeast without giving precursor; (iii) estimate novel pathways with considering several categories, including enzyme promiscuity, Synthetic Complex Score (SCScore) and LD50 of intermediates, overall stoichiometric conversions, pathway length, theoretical yields and thermodynamic feasibility. According to the results, novoPathFinder is more capable to recover experimentally validated pathways when comparing other rule-based web server tools. Besides, more efficient pathways with novel reactions could also be retrieved for further experimental exploration. novoPathFinder is available at http://design.rxnfinder.org/novopathfinder/.

RxnBLAST: molecular scaffold and reactive chemical environment feature extractor for biochemical reactions.

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/.

EnzyMine: a comprehensive database for enzyme function annotation with enzymatic reaction chemical feature.

Addition of chemical structural information in enzymatic reactions has proven to be significant for accurate enzyme function prediction. However, such chemical data lack systematic feature mining and hardly exist in enzyme-related databases. Therefore, global mining of enzymatic reactions will offer a unique landscape for researchers to understand the basic functional mechanisms of natural bioprocesses and facilitate enzyme function annotation. Here, we established a new knowledge base called EnzyMine, through which we propose to elucidate enzymatic reaction features and then link them with sequence and structural annotations. EnzyMine represents an advanced database that extends enzyme knowledge by incorporating reaction chemical feature strategies, strengthening the connectivity between enzyme and metabolic reactions. Therefore, it has the potential to reveal many new metabolic pathways involved with given enzymes, as well as expand enzyme function annotation. Database URL: http://www.rxnfinder.org/enzymine/.

AdditiveChem: A comprehensive bioinformatics knowledge-base for food additive chemicals.

Food additives are considered to be the catalysts and headstones of the modern food industry, affecting every step of food production, processing, and storage. The urgent need for a comprehensive curation of food additives, including their molecular structures, biological activities, and precise toxicological evaluations, prompted the creation of the AdditiveChem database (http://www.rxnfinder.org/additivechem/). This database has curated >9064 types of food additives, along with their molecular structure, chemical and physical properties, absorption, distribution, metabolism, excretion and toxicity properties, biosynthesis and biodegradation methods, usage specifications, toxicological and risk assessment data, and targets in the human body from 16 databases to construct an efficient search platform for in silico preliminary evaluations. AdditiveChem database will enable an exploration of the relationship between the structure and function of food additives.

FRCD: A comprehensive food risk component database with molecular scaffold, chemical diversity, toxicity, and biodegradability analysis.

The presence of natural toxins, pesticide residues, and illegal additives in food products has been associated with a range of potential health hazards. However, no systematic database exists that comprehensively includes and integrates all research information on these compounds, and valuable information remains scattered across numerous databases and extensive literature reports. Thus, using natural language processing technology, we curated 12,018 food risk components from 152,737 literature reports, 12 authoritative databases, and numerous related regulatory documents. Data on molecular structures, physicochemical properties, chemical taxonomy, absorption, distribution, metabolism, excretion, toxicity properties, and physiological targets within the human body were integrated to afford the comprehensive food risk component database (FRCD, http://www.rxnfinder.org/frcd/). We also analyzed the molecular scaffold and chemical diversity, in addition to evaluating the toxicity and biodegradability of the food risk components. The FRCD could be considered a highly promising tool for future food safety studies.

CF-Targeter: A Rational Biological Cell Factory Targeting Platform for Biosynthetic Target Chemicals.

Biosynthesis is a promising method for chemical synthesis. However, due to varieties between different microorganism hosts, yield and heterologous pathways needed for production of target chemical may also vary from different strains. One of the main challenges in metabolic engineering is to select an appropriate chassis host for specified target chemical production. However, with thousands of microorganisms existing in nature and extremely complicated metabolism within them, it is still time-consuming and error-prone work to achieve such a goal only through experimental methods, even with some existing computational methods. Hence, more efficient methods should be proposed to assist in selecting appropriate chassis hosts. In this article, based on symbolic reaction repositories and a pathway search algorithm which performed 1 400 000 searches for per target compound, we established a biological reasoning system for appropriate chassis host selection by coupling with various GEM-models. By using a supercomputer to calculate the biosynthetic pathways for more than 1 month, nearly 50 000 000 biosynthetic pathways are computed for production of 6026 compounds within 70 microorganisms. With retrieved organisms for specified target production, several heterologous biosynthetic pathways can be shown in length order, and then the maximum theoretical yields and thermodynamic feasibility can be calculated in real time under customized growth conditions and physiological states. From the computation results, the system not only identifies experimentally validated pathways but also outputs more efficient solutions with less heterologous steps or higher maximum possible theoretical yield by engineering other organism hosts. CF-targeter is available at http://www.rxnfinder.org/cf_targeter/.