Draft Genome Sequences of the Obligatory Marine Myxobacterial Strains Enhygromyxa salina SWB005 and SWB007

The two marine myxobacterial strains Enhygromyxa salina SWB005 and SWB007 were isolated from coastal soil samples using Escherichia coli as bait for these predatory strains. These strains produce unique specialized metabolites. Genomes were assembled into 312 contigs for E. salina SWB005 (9.0 Mbp) and 192 contigs for E. salina SWB007 (10.6 Mbp)

MIBiG 2.0: a repository for biosynthetic gene clusters of known function

Fueled by the explosion of (meta)genomic data, genome mining of specialized metabolites has become a major technology for drug discovery and studying microbiome ecology. In these efforts, computational tools like antiSMASH have played a central role through the analysis of Biosynthetic Gene Clusters (BGCs). Thousands of candidate BGCs from microbial genomes have been identified and stored in public databases. Interpreting the function and novelty of these predicted BGCs requires comparison with a well-documented set of BGCs of known function. The MIBiG (Minimum Information about a Biosynthetic Gene Cluster) Data Standard and Repository was established in 2015 to enable curation and storage of known BGCs. Here, we present MIBiG 2.0, which encompasses major updates to the schema, the data, and the online repository itself. Over the past five years, 851 new BGCs have been added. Additionally, we performed extensive manual data curation of all entries to improve the annotation quality of our repository. We also redesigned the data schema to ensure the compliance of future annotations. Finally, we improved the user experience by adding new features such as query searches and a statistics page, and enabled direct link-outs to chemical structure databases. The repository is accessible online at https://mibig.secondarymetabolites.org/

Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species

Background Genome mining tools have enabled us to predict biosynthetic gene clusters that might encode compounds with valuable functions for industrial and medical applications. With the continuously increasing number of genomes sequenced, we are confronted with an overwhelming number of predicted clusters. In order to guide the effective prioritization of biosynthetic gene clusters towards finding the most promising compounds, knowledge about diversity, phylogenetic relationships and distribution patterns of biosynthetic gene clusters is necessary. Results Here, we provide a comprehensive analysis of the model actinobacterial genus Amycolatopsis and its potential for the production of secondary metabolites. A phylogenetic characterization, together with a pan-genome analysis showed that within this highly diverse genus, four major lineages could be distinguished which differed in their potential to produce secondary metabolites. Furthermore, we were able to distinguish gene cluster families whose distribution correlated with phylogeny, indicating that vertical gene transfer plays a major role in the evolution of secondary metabolite gene clusters. Still, the vast majority of the diverse biosynthetic gene clusters were derived from clusters unique to the genus, and also unique in comparison to a database of known compounds. Our study on the locations of biosynthetic gene clusters in the genomes of Amycolatopsis’ strains showed that clusters acquired by horizontal gene transfer tend to be incorporated into non-conserved regions of the genome thereby allowing us to distinguish core and hypervariable regions in Amycolatopsis genomes. Conclusions Using a comparative genomics approach, it was possible to determine the potential of the genus Amycolatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds

MIBiG 3.0 : a community-driven effort to annotate experimentally validated biosynthetic gene clusters

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/

A biaryl-linked tripeptide from Planomonospora reveals a widespread class of minimal RiPP gene clusters

Microbial natural products impress by their bioactivity, structural diversity, and ingenious biosynthesis. While screening the less exploited actinobacterial genus Planomonospora, two cyclopeptides were discovered, featuring an unusual Tyr-His biaryl bridging across a tripeptide scaffold, with the sequences N-acetyl-Tyr-Tyr-His and N-acetyl-Tyr-Phe-His. Planomonospora genomes pointed toward a ribosomal synthesis of the cyclopeptide from a pentapeptide precursor encoded by 18-bp bytA, to our knowledge the smallest coding gene ever reported. Closely linked to bytA is bytO, encoding a cytochrome P450 monooxygenase likely responsible for biaryl installment. In Streptomyces, the bytAO segment was sufficient to direct production of the crosslinked N-acetylated Tyr-Tyr-His tripeptide. Bioinformatic analysis of related cytochrome P450 monooxygenases indicated that they constitute a widespread family of enzymes, and the corresponding genes are closely linked to 5-amino acid coding sequences in approximately 200 (actino)bacterial genomes, all with potential for biaryl linkage between amino acids 1 and 3. We propose the named biarylitides this family of RiPPs

Genome Analysis of the Marine Bacterium Labrenzia sp. Strain 011, a Potential Protective Agent of Mollusks

The marine bacterium Labrenzia sp. strain 011 was isolated from the coastal sediment of Kronsgaard, Germany. The Labrenzia species are suggested to be protective agents of mollusks. Labrenzia sp. strain 011 produces specialized metabolites, which showed activity against a range of microorganisms, thereunder strong inhibitory effects against Pseudoroseovarius crassostreae DSM 16,950 (genus Roseovarius), the causative agent of oyster disease. The genome of Labrenzia sp. strain 011 was sequenced and assembled into 65 contigs, has a size of 5.1 Mbp, and a G+C content of 61.6%. A comparative genome analysis defined Labrenzia sp. strain 011 as a distinct new species within the genus Labrenzia, whereby 44% of the genome was contributed to the Labrenzia core genome. The genomic data provided here is expected to contribute to a deeper understanding of the mollusk-protective role of Labrenzia spp

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