The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery

Abstract

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, ) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries.

Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

“…2+ ion (representing the isotope containing 113 C atom), and comparison of its MS 2 fragmentation spectrum to the one reported in the literature confirmed this assumption (seeFigures S4 and S31) 25. The lassopeptide sphaericin, identified by the signal m/z 2157.12, corresponding to the [M+H] + ion (representing the isotope containing 1 13 C atom) was found in the extracts of six strains 28.…”

“…7 Tools such as antiSMASH 8 allow to mine genomes for biosynthetic gene clusters (BGC), while BGC repositories such as MIBiG 9 aid in the evaluation of BGC novelty. In addition, advances in (tandem) mass spectrometry and the introduction of molecular networking, 10 the tandem mass (MS 2 ) based grouping of molecules by structural relatedness, has made untargeted metabolomics broadly available, 11 while public databases in the likes of GNPS 12 and the Natural Product Atlas 13 facilitate metabolite annotation. These methods allow to rationalize resources and quickly prioritize strains or metabolites for further investigations.…”

Nematode-Trapping Fungi Produce Diverse Metabolites during Predator–Prey Interaction

“…Metabolomic studies of NTF are still in the infancy, and, therefore, the number of NTF metabolites encompassed in the current metabolomic databases is somewhat lower. For example, we searched the Natural Products Atlas [34], one of the largest public databases of microbial natural products, and found only three metabolites originated from Arthrobotrys fungi. This limitation makes the identification of NTF metabolites very much challenging.…”

Comprehensive database of secondary metabolites from cyanobacteria

“…While information from commercial databases of secondary metabolites are only accessible to paying customers (e.g., Antibase, MarinLit, The Dictionary of Natural Products), several open-access databases exist but are often limited regarding the number cyanobacterial metabolites or parameters listed (e.g., ALGALTOX List, NORINE database, Handbook of Marine Natural Products). [2][3][4] Some key open access databases are listed in Table 1. The "Cyanomet mass" list by LeManach et al (2019) contains 852 entries, of which 35 belong to the class of microcystins and nearly 500 compounds are listed with complete molecular formulae and literature reference but no further structural information is given.…”

“…3 The Natural Product Atlas (2019) contains a similar number of entries for cyanobacterial metabolites, including microcystins, and also provides structural codes (e.g., SMILES code) and the stereochemistry is known for 768 entries (isomeric SMILES code). 4 In 2017 the Handbook of Cyanobacterial Monitoring and Cyanotoxin Analysis published a list of 246 microcystins. 5 Today, the most comprehensive list of microcystins and nodularins is curated by Miles et al and was recently updated (2019) to include 279 microcystin variants with molecular formulae, references and a systematic naming system implying the structural compositions but no structural codes were provided.…”