The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data.
Despite decades of cultivating microorganisms for use in drug discovery, few attempts have been made to measure the extent to which common cultivation techniques have accessed existing chemical space. Metagenomic studies have shown that cultivable bacteria represent a fraction of those that exist in the environment, and that uncultivated populations in sediment have genes that encode for a high diversity of novel natural product (NP) biosynthetic enzymes. Quantifying these genes in both sediment and cultivatable bacterial populations allows us to assess how much diversity is present on nutrient agar and is critical to guiding the trajectory of future NP discovery platforms. Herein, we employed next-generation amplicon sequencing to assess the NP biosynthetic gene populations present in two Lake Huron sediment samples, and compared these with populations from their corresponding cultivatable bacteria. We highlight three findings from our study: (1) after cultivation, we recovered between 7.7% and 23% of three common types of NP biosynthetic genes from the original sediment population; (2) between 76.3% and 91.5% of measured NP biosynthetic genes from nutrient agar have yet to be characterized in known biosynthetic gene cluster databases, indicating that readily cultivatable bacteria harbor the potential to produce new NPs; and (3) even though the predominant taxa present on nutrient media represented some of the major producers of bacterial NPs, the sediment harbored a significantly greater pool of NP biosynthetic genes that could be mined for structural novelty, and these likely belong to taxa that typically have not been represented in microbial drug discovery libraries.
Wastewater treatment plants (WWTPs) are known to harbor antibiotic resistance genes (ARGs) that are disseminated into the environment via effluent. However, few studies have compared abundance, mobilization and selective pressures for ARGs in WWTPs as a function of variations in secondary treatment bioprocesses. We used shotgun metagenomics to provide a comprehensive analysis of ARG composition, relationship to mobile genetic elements and co-occurrences with antibiotic production genes (APGs) throughout two full-scale municipal WWTPs, one of which employs biofilm-based secondary treatment and another that uses a suspended growth system. Results showed that abundances of ARGs declined by over 90% per genome equivalent in both types of wastewater treatment processes. However, the fractions of ARGs associated with mobile genetic elements increased substantially between influent and effluent in each plant, indicating significant mobilization of ARGs throughout both treatment processes. Strong positive correlations between ARGs and APGs were found for the aminoglycoside antibiotic class in the suspended growth system and for the streptogramin antibiotic class in the biofilm system. The biofilm and suspended growth WWTPs exhibited similarities in ARG abundances, composition and mobilization trends. However, clear differences were observed for within-plant ARG persistence. These findings suggest that both biofilm and suspended growth-based WWTPs may promote genetic mobilization of persistent ARGs that are then disseminated in effluent to receiving water bodies.
− Compared to their terrestrial and marine counterparts, little is known about the capacity of freshwater-derived actinomycete bacteria to produce novel secondary metabolites. In the current study, we highlight the disparities that exist between cultivation-independent and -dependent analyses of actinomycete communities from four locations in Lake Michigan sediment. Furthermore, through phylogenetic analysis of strains isolated from these locations, we identified a Streptomyces sp., strain B025, as being distinct from other Streptomyces spp. isolated from sediment. Upon fermentation this strain produced a rare class of eightmembered lactone secondary metabolites, which have been for their antitumor properties. We used spectroscopic and chemical derivitization techniques to characterize octalactin B (1) in addition to its corresponding novel, unnatural degradation product (2).
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