Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

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

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

Myxobacteria are famous for their ability to produce most intriguing secondary metabolites. Till recently, only terrestrial myxobacteria were in the focus of research. In this review, however, we discuss marine-derived myxobacteria, which are particularly interesting due to their relatively recent discovery and due to the fact that their very existence was called into question. The to-date-explored members of these halophilic or halotolerant myxobacteria are all grouped into the suborder Nannocystineae. Few of them were chemically investigated revealing around 11 structural types belonging to the polyketide, non-ribosomal peptide, hybrids thereof or terpenoid class of secondary metabolites. A most unusual structural type is represented by salimabromide from Enhygromyxa salina. In silico analyses were carried out on the available genome sequences of four bacterial members of the Nannocystineae, revealing the biosynthetic potential of these bacteria

Manipulation of Regulatory Genes Reveals Complexity and Fidelity in Hormaomycin Biosynthesis

Hormaomycin (HRM) is a structurally remarkable peptide produced by Streptomyces griseoflavus W-384 that acts as a Streptomyces signaling metabolite and exhibits potent antibiotic activity against coryneform actinomycetes. HRM biosynthetic studies have been hampered by inconsistent and low production. To enhance fermentation titers, the role of its cluster-encoded regulatory genes was investigated. Extra copies of the putative regulators hrmA and hrmB were introduced into the wild-type strain, resulting in an increase of HRM production and its analogs up to 135-fold. For the HrmB overproducer, six bioactive analogs were isolated and characterized. This study demonstrates that HrmA and HrmB are positive regulators in HRM biosynthesis. A third gene, hrmH, was identified as encoding a protein capable of shifting the metabolic profile of HRM and its derivatives. Its manipulation resulted in the generation of an additional HRM analog

Analysis of the Genome and Metabolome of Marine Myxobacteria Reveals High Potential for Biosynthesis of Novel Specialized Metabolites

Abstract Comparative genomic/metabolomic analysis is a powerful tool to disclose the potential of microbes for the biosynthesis of novel specialized metabolites. In the group of marine myxobacteria only a limited number of isolated species and sequenced genomes is so far available. However, the few compounds isolated thereof so far show interesting bioactivities and even novel chemical scaffolds; thereby indicating a huge potential for natural product discovery. In this study, all marine myxobacteria with accessible genome data (n = 5), including Haliangium ochraceum DSM 14365, Plesiocystis pacifica DSM 14875, Enhygromyxa salina DSM 15201 and the two newly sequenced species Enhygromyxa salina SWB005 and SWB007, were analyzed. All of these accessible genomes are large (~10 Mb), with a relatively small core genome and many unique coding sequences in each strain. Genome analysis revealed a high variety of biosynthetic gene clusters (BGCs) between the strains and several resistance models and essential core genes indicated the potential to biosynthesize antimicrobial molecules. Polyketides (PKs) and terpenes represented the majority of predicted specialized metabolite BGCs and contributed to the highest share between the strains. BGCs coding for non-ribosomal peptides (NRPs), PK/NRP hybrids and ribosomally synthesized and post-translationally modified peptides (RiPPs) were mostly strain specific. These results were in line with the metabolomic analysis, which revealed a high diversity of the chemical features between the strains. Only 6–11% of the metabolome was shared between all the investigated strains, which correlates to the small core genome of these bacteria (13–16% of each genome). In addition, the compound enhygrolide A, known from E. salina SWB005, was detected for the first time and structurally elucidated from Enhygromyxa salina SWB006. The here acquired data corroborate that these microorganisms represent a most promising source for the detection of novel specialized metabolites

Diversity and Antimicrobial Potential of Predatory Bacteria from the Peruvian Coastline

The microbiome of three different sites at the Peruvian Pacific coast was analyzed, revealing a lower bacterial biodiversity at Isla Foca than at Paracas and Manglares, with 89 bacterial genera identified, as compared to 195 and 173 genera, respectively. Only 47 of the bacterial genera identified were common to all three sites. In order to obtain promising strains for the putative production of novel antimicrobials, predatory bacteria were isolated from these sampling sites, using two different bait organisms. Even though the proportion of predatory bacteria was only around 0.5% in the here investigated environmental microbiomes, by this approach in total 138 bacterial strains were isolated as axenic culture. 25% of strains showed antibacterial activity, thereby nine revealed activity against clinically relevant methicillin resistant Staphylococcus aureus (MRSA) and three against enterohemorrhagic Escherichia coli (EHEC) strains. Phylogeny and physiological characteristics of the active strains were investigated. First insights into the chemical basis of the antibacterial activity indicated the biosynthetic production of the known compounds ariakemicin, kocurin, naphthyridinomycin, pumilacidins, resistomycin, and surfactin. However, most compounds remained elusive until now. Hence, the obtained results implicate that the microbiome present at the various habitats at the Peruvian coastline is a promising source for heterotrophic bacterial strains showing high potential for the biotechnological production of antibiotics