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.

Major advances in genome sequencing and large-scale biosynthetic gene cluster (BGC) analysis have prompted an age of natural product discovery driven by genome mining. Still, connecting molecules to their cognate BGCs is a substantial bottleneck for this approach. We have developed a mass spectrometry-based parallel stable isotope labeling platform, termed IsoAnalyst, which assists in associating metabolite stable isotope labeling patterns with BGC structure prediction in order to connect natural products to their corresponding BGCs. Here we show that IsoAnalyst can quickly associate both known metabolites and unknown analytes with BGCs to elucidate the complex chemical phenotypes of these biosynthetic systems. We validate this approach for a range of compound classes, using both the type strain Saccharopolyspora erythraea and an environmentally isolated Micromonospora sp. We further demonstrated the utility of this tool with the discovery of lobosamide D, a new and structurally unique member of the family of lobosamide macrolactams.

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Yellowjackets in the genera Vespula and Dolichovespula are prevalent eusocial insects of great ecological and economic significance, but the chemical signals of their sexual communication systems have defied structural elucidation. Herein, we report the identification of sex attractant pheromone components of virgin bald-faced hornet queens (Dolichovespula maculata). We analyzed body surface extracts of queens by coupled gas chromatographic-electroantennographic detection (GC-EAD), isolated the compounds that elicited responses from male antennae by high-performance liquid chromatography (HPLC), and identified these components by GC mass spectrometry (MS), HPLC-MS, and NMR spectroscopy. In laboratory olfactometer experiments, synthetic (2Z,7E)-3,7-dimethyldeca-2,7-diendioic acid (termed here maculatic acid A) and (2Z,7E)-10-methoxy-3,7-dimethyldeca-10-oxo-deca-2,7-dienoic acid (termed here maculatic acid C) in binary combination significantly attracted bald-faced hornet males. These are the first sex attractant pheromone components identified in yellowjackets.

As part of an ongoing program to identify sex attractant pheromone components that mediate sexual communication in yellowjacket wasps, a novel sesquiterpene was isolated from body surface extracts of virgin bald-faced hornet queens, Dolichovespula maculata. The gross structure of this sesquiterpene was proposed through microscale spectroscopic analyses, and the configuration of the central olefin was subsequently confirmed by total synthesis. This new natural product (termed here dolichovespulide) represents an important addition to the relatively small number of terpenoids reported from the taxonomic insect family Vespidae.