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As a result of the continuous evolution of drug resistant bacteria, new antibiotics are urgently needed. Encoded by biosynthetic gene clusters (BGCs), antibiotic compounds are mostly produced by bacteria. With the exponential increase in the number of publicly available, sequenced genomes and the advancements of BGC prediction tools, genome mining algorithms have uncovered millions of uncharacterized BGCs for further evaluation. Since compound identification and characterization remain bottlenecks, a major challenge is prioritizing promising BGCs. Recently, researchers adopted self-resistance based strategies allowing them to predict the biological activities of natural products encoded by uncharacterized BGCs. Since 2017, the Antibiotic Resistant Target Seeker (ARTS) facilitated this so-called target-directed genome mining (TDGM) approach for the prioritization of BGCs encoding potentially novel antibiotics. Here, we present the ARTS database, available at https://arts-db.ziemertlab.com/. The ARTS database provides pre-computed ARTS results for >70,000 genomes and metagenome assembled genomes in total. Advanced search queries allow users to rapidly explore the fundamental criteria of TDGM such as BGC proximity, duplication and horizontal gene transfers of essential housekeeping genes. Furthermore, the ARTS database provides results interconnected throughout the bacterial kingdom as well as links to known databases in natural product research., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The development of new antibacterial drugs has become one of the most important tasks of the century in order to overcome the posing threat of drug resistance in pathogenic bacteria. Many antibiotics originate from natural products produced by various microorganisms. Over the last decades, bioinformatical approaches have facilitated the discovery and characterization of these small compounds using genome mining methodologies. A key part of this process is the identification of the most promising biosynthetic gene clusters (BGCs), which encode novel natural products. In 2017, the Antibiotic Resistant Target Seeker (ARTS) was developed in order to enable an automated target-directed genome mining approach. ARTS identifies possible resistant target genes within antibiotic gene clusters, in order to detect promising BGCs encoding antibiotics with novel modes of action. Although ARTS can predict promising targets based on multiple criteria, it provides little information about the cluster structures of possible resistant genes. Here, we present SYN-view. Based on a phylogenetic approach, SYN-view allows for easy comparison of gene clusters of interest and distinguishing genes with regular housekeeping functions from genes functioning as antibiotic resistant targets. Our aim is to implement our proposed method into the ARTS web-server, further improving the target-directed genome mining strategy of the ARTS pipeline.

Multi-drug resistant pathogens have become a major threat to human health and new antibiotics are urgently needed. Most antibiotics are derived from secondary metabolites produced by bacteria. In order to avoid suicide, these bacteria usually encode resistance genes, in some cases within the biosynthetic gene cluster (BGC) of the respective antibiotic compound. Modern genome mining tools enable researchers to computationally detect and predict BGCs that encode the biosynthesis of secondary metabolites. The major challenge now is the prioritization of the most promising BGCs encoding antibiotics with novel modes of action. A recently developed target-directed genome mining approach allows researchers to predict the mode of action of the encoded compound of an uncharacterized BGC based on the presence of resistant target genes. In 2017, we introduced the 'Antibiotic Resistant Target Seeker' (ARTS). ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets by rapidly linking housekeeping and known resistance genes to BGC proximity, duplication and horizontal gene transfer (HGT) events. Here, we present ARTS 2.0 available at http://arts.ziemertlab.com. ARTS 2.0 now includes options for automated target directed genome mining in all bacterial taxa as well as metagenomic data. Furthermore, it enables comparison of similar BGCs from different genomes and their putative resistance genes., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)