FunARTS, the Fungal bioActive compound Resistant Target Seeker, an exploration engine for target-directed genome mining in fungi

Abstract

There is an urgent need to diversify the pipeline for discovering novel natural products due to the increase in multi-drug resistant infections. Like bacteria, fungi also produce secondary metabolites that have potent bioactivity and rich chemical diversity. To avoid self-toxicity, fungi encode resistance genes which are often present within the biosynthetic gene clusters (BGCs) of the corresponding bioactive compounds. Recent advances in genome mining tools have enabled the detection and prediction of BGCs responsible for the biosynthesis of secondary metabolites. The main challenge now is to prioritize the most promising BGCs that produce bioactive compounds with novel modes of action. With target-directed genome mining methods, it is possible to predict the mode of action of a compound encoded in an uncharacterized BGC based on the presence of resistant target genes. Here, we introduce the 'fungal bioactive compound resistant target seeker' (FunARTS) available at https://funarts.ziemertlab.com. This is a specific and efficient mining tool for the identification of fungal bioactive compounds with interesting and novel targets. FunARTS rapidly links housekeeping and known resistance genes to BGC proximity and duplication events, allowing for automated, target-directed mining of fungal genomes. Additionally, FunARTS generates gene cluster networking by comparing the similarity of BGCs from multi-genomes.