Biology subjects

Marner, M.

Publications and source records attributed to Marner, M..

3 recordsLinked to original sources

bioRxiv2025

Tryptophan-Driven Metabolomic Shift in Acidobacteriaceae Reveals Phytohormones and Antifungal Metabolites

Acidobacteriota is one of the most abundant phyla in soils and has recently attracted attention for its potential role in promoting phytosanitary benefits. The metabolomic capabilities of this phylum remain poorly characterised, with few experimentally confirmed metabolites described. To address these gaps, we combined metabolomic profiling with comparative genomic analysis to explore the functional potential of novel strains within the Acidobacteriaceae family. Genome mining across the phylum for plant-growth-promoting traits revealed the presence and taxon-specific enrichment of genes related to phytohormone production, as well as other genes associated with plant-beneficial microorganisms. When tryptophan was added to the cultivation medium, it triggered a strong metabolic response in the strains, resulting in measurable changes in the production levels of phytohormones such as indole-3-acetic acid and indole-3-pyruvate. Building on these findings, we examined the metabolic reprogramming caused by tryptophan supplementation, which suppressed the growth of phytopathogenic fungi, leading to the identification of malassezindoles and pityriacitrins as active agents. This was confirmed by isolating and elucidating the structure of pityriacitrin B and one of its methyl esters through NMR studies. Overall, these findings shed light on the previously unexplored metabolic potential of the Acidobacteriota phylum, emphasising its ecological importance for phytosanitary applications. ImportanceDespite their ubiquity and genomic diversity, the functional metabolism of members of the Acidobacteriota has largely remained uncharacterised. This study links genomic predictions to experimentally verified metabolomic outputs of Acidobacteriaceae, demonstrating tryptophan-responsive metabolic shifts translating to phytohormones and metabolites suppressing fungal growth. Our work underscores the emerging role of Acidobacteriota as important contributors to soil ecosystem functioning and plant-microbe interactions.

microbiology↗

bioRxiv2024

Nanoliter-scale selection of optimized bioengineered peptide antibiotics that rescue mice with bacterial lung infection

Increasing numbers of multi-drug resistant pathogens call for new chemical scaffolds, addressing novel targets, that can serve as lead structures for the development of life-saving drugs. For antibiotics, natural product-inspired molecules represent a most promising resource. Natural products evolved to high chemical complexity and occupy a chemical space different than synthetic libraries. However, clinical translation of promising natural products is often impeded by their relative inaccessibility to medicinal chemistry optimization, e.g. iterative synthesis of large series of derivatives. Here, this limitation is addressed with a randomized library of bicyclic heptapeptides based on the natural product darobactin that hits the clinically not addressed target BamA. Variants of the ribosomally synthesized and post-translationally modified peptides were generated using heterologous mutasynthesis. A parallelized screening assay is adapted in nanoliter-scale beads to test the darobactin derivatives against our sensor strain. Loss of fluorescence sorting prioritized 563 events out of the analyzed [~]500k beads. Re-testing confirmed 48 hit events, of which 40 proved to produce distinct darobactin-type molecules. Most promising structures were isolated and the growth inhibitory effects against Gram-negative pathogens validated. One of our current frontrunner compounds (i.e., darobactin B) was reinforced by the randomized screen. While microbiological investigations of the new derivatives is ongoing, darobactin B was profiled in later tier assays and compared to another promising, rationally-designed analog (i.e., darobactin B9, "D22"). Early ADMET profiling and efficacy tests in a mouse pneumonia model were performed. Darobactin B reduced bacterial load of Pseudomonas aeruginosa and Klebsiella pneumoniae by intraperitoneal, as well as intratracheal administration. Our study showcases the potential of mutasynthetic libraries for high-throughput screening and identification of functional peptides for drug lead discovery.

microbiology↗

bioRxiv2021

Genomic and chemical decryption of the Bacteroidetes phylum for its potential to biosynthesize natural products

With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining - using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis and rating - has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of peerless strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Sourcing this dataset, we isolated the new iron chelating nonribosomally-synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively. TeaserCombination of omics-technologies revealed taxonomical hotspots for specialized metabolites within Bacteroidetes.

microbiology↗