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.

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/.

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.

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.

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/.

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.

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: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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.