NPClassifier: A Deep Neural Network-Based Structural Classification Tool for Natural Products.

Computational approaches such as genome and metabolome mining are becoming essential to natural products (NPs) research. Consequently, a need exists for an automated structure-type classification system to handle the massive amounts of data appearing for NP structures. An ideal semantic ontology for the classification of NPs should go beyond the simple presence/absence of chemical substructures, but also include the taxonomy of the producing organism, the nature of the biosynthetic pathway, and/or their biological properties. Thus, a holistic and automatic NP classification framework could have considerable value to comprehensively navigate the relatedness of NPs, and especially so when analyzing large numbers of NPs. Here, we introduce NPClassifier, a deep-learning tool for the automated structural classification of NPs from their counted Morgan fingerprints. NPClassifier is expected to accelerate and enhance NP discovery by linking NP structures to their underlying properties.

Cyanobacteria-shrimp colonies in the Mariana Islands.

Cyanobacteria have multifaceted ecological roles on coral reefs. Moorena bouillonii, a chemically rich filamentous cyanobacterium, has been characterized as a pathogenic organism with an unusual ability to overgrow gorgonian corals, but little has been done to study its general growth habits or its unique association with the snapping shrimp Alpheus frontalis. Quantitative benthic surveys, and field and photographic observations were utilized to develop a better understanding of the ecology of these species, while growth experiments and nutrient analysis were performed to examine how this cyanobacterium may be benefiting from its shrimp symbiont. Colonies of M. bouillonii and A. frontalis displayed considerable habitat specificity in terms of occupied substrate. Although found to vary in abundance and density across survey sites and transects, M. bouillonii was consistently found to be thriving with A. frontalis within interstitial spaces on the reef. Removal of A. frontalis from cyanobacterial colonies in a laboratory experiment altered M. bouillonii pigmentation, whereas cyanobacteria-shrimp colonies in the field exhibited elevated nutrient levels compared to the surrounding seawater.

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii.

The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS1 feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS2 fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B-J, 2-10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.

Cryptic Species Account for the Seemingly Idiosyncratic Secondary Metabolism of Sarcophyton glaucum Specimens Collected in Palau.

Sarcophyton glaucum is one of the most abundant and chemically studied soft corals with over 100 natural products reported in the literature, primarily cembrane diterpenoids. Yet, wide variation in the chemistry observed from S. glaucum over the past 50 years has led to its reputation as a capricious producer of bioactive metabolites. Recent molecular phylogenetic analysis revealed that S. glaucum is not a single species but a complex of at least seven genetically distinct species not distinguishable using traditional taxonomic criteria. We hypothesized that perceived intraspecific chemical variation observed in S. glaucum was actually due to differences between cryptic species (interspecific variation). To test this hypothesis, we collected Sarcophyton samples in Palau, performed molecular phylogenetic analysis, and prepared chemical profiles of sample extracts using gas chromatography-flame ionization detection. Both unsupervised (principal component analysis) and supervised (linear discriminant analysis) statistical analyses of these profiles revealed a strong relationship between cryptic species membership and chemical profiles. Liquid chromatography with tandem mass spectrometry-based analysis using feature-based molecular networking permitted identification of the chemical drivers of this difference between clades, including cembranoid diterpenes (2R,11R,12R)-isosarcophytoxide (5), (2S,11R,12R)-isosarcophytoxide (6), and isosarcophine (7). Our results suggest that early chemical studies of Sarcophyton may have unknowingly conflated different cryptic species of S. glaucum, leading to apparently idiosyncratic chemical variation.

Mass Spectrometry-Based Visualization of Molecules Associated with Human Habitats.

The cars we drive, the homes we live in, the restaurants we visit, and the laboratories and offices we work in are all a part of the modern human habitat. Remarkably, little is known about the diversity of chemicals present in these environments and to what degree molecules from our bodies influence the built environment that surrounds us and vice versa. We therefore set out to visualize the chemical diversity of five built human habitats together with their occupants, to provide a snapshot of the various molecules to which humans are exposed on a daily basis. The molecular inventory was obtained through untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of samples from each human habitat and from the people that occupy those habitats. Mapping MS-derived data onto 3D models of the environments showed that frequently touched surfaces, such as handles (e.g., door, bicycle), resemble the molecular fingerprint of the human skin more closely than other surfaces that are less frequently in direct contact with humans (e.g., wall, bicycle frame). Approximately 50% of the MS/MS spectra detected were shared between people and the environment. Personal care products, plasticizers, cleaning supplies, food, food additives, and even medications that were found to be a part of the human habitat. The annotations indicate that significant transfer of chemicals takes place between us and our built environment. The workflows applied here will lay the foundation for future studies of molecular distributions in medical, forensic, architectural, space exploration, and environmental applications.