ChemFOnt: the chemical functional ontology resource

Abstract

The Chemical Functional Ontology (ChemFOnt), located at https://www.chemfont.ca, is a hierarchical, OWL-compatible ontology describing the functions and actions of >341 000 biologically important chemicals. These include primary metabolites, secondary metabolites, natural products, food chemicals, synthetic food additives, drugs, herbicides, pesticides and environmental chemicals. ChemFOnt is a FAIR-compliant resource intended to bring the same rigor, standardization and formal structure to the terms and terminology used in biochemistry, food chemistry and environmental chemistry as the gene ontology (GO) has brought to molecular biology. ChemFOnt is available as both a freely accessible, web-enabled database and a downloadable Web Ontology Language (OWL) file. Users may download and deploy ChemFOnt within their own chemical databases or integrate ChemFOnt into their own analytical software to generate machine readable relationships that can be used to make new inferences, enrich their omics data sets or make new, non-obvious connections between chemicals and their direct or indirect effects. The web version of the ChemFOnt database has been designed to be easy to search, browse and navigate. Currently ChemFOnt contains data on 341 627 chemicals, including 515 332 terms or definitions. The functional hierarchy for ChemFOnt consists of four functional ‘aspects’, 12 functional super-categories and a total of 173 705 functional terms. In addition, each of the chemicals are classified into 4825 structure-based chemical classes. ChemFOnt currently contains 3.9 million protein-chemical relationships and ∼10.3 million chemical-functional relationships. The long-term goal for ChemFOnt is for it to be adopted by databases and software tools used by the general chemistry community as well as the metabolomics, exposomics, metagenomics, genomics and proteomics communities.

NMR-Metabolomic Profiling and Genome Mining Drive the Discovery of Cyclic Decapeptides from a Marine Streptomyces

“…Analysis of the NRPS domains of len revealed ten A domains, which is consistent with the number of amino acid residues in the lenziamide backbone. However, the predicted substrates (Val 1 , Pro 5 , Gln 7 , Val 9 , and Leu 10 ) activated by the A domains of modules 1, 5, 7, 9, and 10 in the len BGC are not consistent with the NMR-assigned residues (Ala 1 , Piz 5 , Val 7 /Ile 7 , β-Ala 9 , and Val 10 ) in 1 and 2 (Table S5). The nonproteinogenic Piz 5 in lenziamides is proposed to be synthesized by putative piperazate synthases LenE (Orf25) and LenF (Orf26) using ornithine as a substrate (Figure 6C).…”

“…S063 was proposed based on the bioinformatics and structural analysis, with 13 continuous NRPS genes of the len BGC credited with constructing the lenziamide backbone. Significant attention has been paid to precursor biosynthesis involved in two nonproteinogenic residues Piz 5 and β-Ala 9 . These findings set the stage for the full characterization of the biosynthetic mechanisms of lenziamide production.…”

“…7 NMRmetabolomic profiling enables simultaneous structural assignments of compound mixtures to gain an insight into the molecular types and purity of the metabolites in a sample under investigation. 8,9 As an alternative approach for natural product discovery, genome mining, which connects genotype to chemotype, provides the biosynthetic capacity of diverse secondary metabolites in microorganisms and enables the prediction of the structures. 10 The integration of NMRmetabolomic and genomic data sets can provide enhanced identification of structural properties as well as key biosynthetic information, thus achieving targeted discovery of new natural products.…”

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

“…For drug development PubChem is a foundational resource and its update here ( 83 ) reports on 120 new data sources, with patent coverage particularly strengthened. In the same area ChemFOnt ( 84 ) brings a new hierarchical ontology describing functions of biologically important chemicals. Major returning resources for drugs and their targets include DrugCentral ( 85 ), which now covers veterinary drugs too and has new data on adverse drug events, and TCRD/Pharos ( 86 ) which has incorporated fresh data sources and new data visualisations such as clever circular treemaps to intuitively map expression onto ontologies.…”

Computational Approaches to Enzyme Inhibition by Marine Natural Products in the Search for New Drugs

“…The functional hierarchy within ChemFOnt consists of four functional “aspects” (physiological effect; disposition; process; and role), which are subdivided into twelve functional categories (health effects and organoleptic effects; sources, biological locations, and routes of exposure; environmental, natural, and industrial processes; adverse biological roles, normal biological roles, environmental roles, and industrial applications) and a total of >170,000 functional terms. At the time of publishing, ChemFOnt contained almost four million protein-chemical relationships and more than ten million chemical-functional relationships that can be adopted by other databases and software tools and be of utility not only to general chemists but also to researchers involved in genomics, metagenomics, proteomics, and metabolomics [ 92 ].…”