Biology subjects

Zdouc, M. M.

Publications and source records attributed to Zdouc, M. M..

6 recordsLinked to original sources

bioRxiv2025

Charting the biosynthetic landscape of hybrid polyketide-nonribosomal peptide-specialized lipids

Polyunsaturated fatty acid (PUFA) synthase-like enzymes are best known for their role in membrane lipid biosynthesis in marine bacteria, but have also been repurposed for the assembly of specialized lipid metabolites with unique biological functions. Here, we illuminate their broader biosynthetic potential by charting the unexplored landscape of hybrid peptide-polyketide-specialized lipid biosynthesis in bacteria. Using a targeted genome mining strategy, we identified more than 60 biosynthetic gene clusters that combine PUFA synthase-like, polyketide synthase (PKS), and nonribosomal peptide synthetase (NRPS) enzymes across diverse bacterial lineages. Comparative analysis revealed extensive diversification of these triple hybrid pathways through gene fusion, domain reshuffling and recruitment of accessory enzymes. We further expand the known repertoire of peptide-polyketide-specialized lipid hybrids by identifying the chitinimines, a new family of amphiphilic metabolites produced by Chitinimonas koreensis featuring a C22 polyunsaturated lipid chain conjugated to a cyclic peptide-polyketide and a pyruvate-derived cyclic acetal moiety. The chitinimines exhibit surfactant properties, as well as moderate antibacterial activity against Gram-positive bacteria and contribute to a growth-promoting interaction between C. koreensis and Salmonella spp. Together, these findings demonstrate that PUFA synthase-like systems are far more versatile than previously appreciated, playing a key role in combinatorial biosynthetic innovation and serving as a rich, untapped source of chemically and functionally diverse specialized lipids.

microbiology↗

bioRxiv2024

Olive mill solid waste induces beneficial mushroom-specialized metabolite diversity: a computational metabolomics study.

IntroductionMushrooms contain besides proteins a diverse pallet of specialized metabolites bioactive in either beneficial or harmful manner. Therefore, mushrooms have been exploited by humans for centuries for dietary or medical purposes. For example, the edible and medicinal mushrooms Hericium erinaceus and Pleurotus eryngii are grown commercially around the world. In nature, H. erinaceus grows on old or dead tree trunks, and P. eryngii grows on Apiaceae plant roots, whereas in cultivation, they grow on substrates mainly consisting of dry wood chips, straw, and cereals. To make their farming more sustainable, supplements such as olive mill solid waste (OMSW) have been added to support mushroom development. However, so far, the impact of substrate additives on the edible mushroom metabolic content has not been assessed. MethodsHere, we examined the effect of different proportions of OMSW added to the substrate on the metabolic profiles of the fruiting body (FB) and mycelium of H. erinaceus and P. eryngii mushrooms. We used computational metabolomics strategies including GNPS molecular networking, MS2Query, and the FERMO dashboard, to organize, annotate, and prioritize metabolite features from the untargeted Q-Exactive Plus HR-LC-MS/MS metabolomics data. Following chromatography-based fractionation, the metabolite annotation of four metabolite features was further validated or fine-tuned using 1H-NMR, to resolve structural isomers. Results & DiscussionOur computational metabolomics strategies showed several annotated metabolite features to be affected by OSMW concentration. In general, the methanolic extracts of H. erinaceus FB and mycelium were more highly enriched with specialized metabolites than those of P. eryngii. Interestingly, OMSW increased several hericenone analogues in the H. erinaceus FB, to which beneficial properties, such as anti-inflammatory, anticancer and neuroprotective properties are assigned, as well as several erinacerin metabolites from the mycelium. In addition, high concentrations of OMSW decreased the toxic enniatin metabolite abundance. In conclusion, we demonstrate how a change in substrate composition affects the mushrooms specialized metabolome and can induce beneficial mushroom metabolite diversity. These results highlight the importance of including computational metabolomic strategies to investigate new sustainable growth options for edible mushrooms and other natural foods.

biochemistry↗

bioRxiv2022

FERMO: a Dashboard for Streamlined Rationalized Prioritization of Molecular Features from Mass Spectrometry Data

Small molecules shape phenotypic variation by modulating biological processes, yet linking specific molecules to observed traits remains challenging due to the complexity of biological samples. Liquid chromatography-tandem mass spectrometry routinely detects hundreds of molecules per sample, and computational tools aid in the selection of the biologically relevant subset by organizing, annotating, and integrating orthogonal data. Existing tools typically focus on facilitating data-driven exploration to support manual interpretation, rather than more objective, data-driven prioritization and hypothesis-generation. Here, we introduce FERMO, a free online dashboard interface for prioritization of molecular features and samples associated with phenotypes of interest. FERMOs modular framework automates data processing, annotation, and integration of standardized phenotypic and other metadata. FERMO supports both exploratory and targeted analysis through efficient interactive visualization, reproducible prioritization, and data filtering. We demonstrate FERMOs utility in benchmarking studies prioritizing bioactive compounds from complex biological matrices. FERMO is freely available at https://fermo.bioinformatics.nl/.

bioinformatics↗

bioRxiv2020

Metabolomic investigation of the pseudouridimycin producer, a prolific streptomycete

We report a metabolomic analysis of Streptomyces sp. ID38640, a soil isolate that produces the bacterial RNA polymerase inhibitor pseudouridimycin. The analysis was performed on the wild type and on ten different pum mutants blocked at different steps in pseudouridimycin biosynthesis. The results indicate that Streptomyces sp. ID38640 is able to produce, in addition to pseudouridimcyin, lydicamycins and deferroxiamines, as previously reported, also the lassopeptide ulleungdin, the non-ribosomal peptide antipain and the osmoprotectant ectoine. The corresponding biosynthetic gene clusters were readily identified in the strain genome. We also detected the known compound pyridindolol, for which we propose a previously unreported biosynthetic gene cluster, as well as three families of unknown metabolites. Remarkably, the levels of the different metabolites varied strongly in the different mutant strains, allowing detection of metabolites not normally seen in the wild type. Three newly constructed pum mutants, along with systematic investigation of the accumulated metabolites, shed further lights on pseudouridimycin biosynthesis. We also show that several Streptomyces strains, harboring the pum biosynthetic gene cluster and unrelated to ID38640, readily produce pseudouridimycin.

microbiology↗

bioRxiv2020

A biaryl-linked tripeptide from Planomonospora leads to widespread class of minimal RiPP gene clusters

Microbial natural products impress by their bioactivity, structural diversity and ingenious biosynthesis. While screening the rare actinobacterial genus Planomonospora, cyclopeptides 1A and 1B were discovered, featuring an unusual Tyr-His biaryl-bridging across a tripeptide scaffold, with the sequences N-acetyl-Tyr-Tyr-His (1A) and N-acetyl-Tyr-Phe-His (1B). Genome analysis of the 1A producing strain pointed to-wards a ribosomal synthesis of 1A, from a pentapeptide precursor encoded by the tiny 18-nucleotide gene bycA, to our knowledge the smallest gene ever reported. Further, biaryl instalment is performed by the closely linked gene bycB, encoding a cytochrome P450 monooxygenase. Biosynthesis of 1A was confirmed by heterologous production in Streptomyces, yielding the mature product. Bioinformatic analysis of related cytochrome P450 monooxygenases indicated that they constitute a widespread family of pathways, associated to 5-aa coding sequences in approximately 200 (actino)bacterial genomes, all with potential for a biaryl linkage between amino acids 1 and 3. We propose the name biarylicins for this newly discovered family of RiPPs.

microbiology↗

bioRxiv2020

Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Despite an excellent track record, microbial drug discovery suffers from high rates of re-discovery. Better workflows for the rapid investigation of complex extracts are needed to increase throughput and allow early prioritization of samples. In addition, systematic characterization of poorly explored strains is seldomly performed. Here, we report a metabolomic study of 72 isolates belonging to the rare actinomycete genus Planomonospora, using a workflow of open access tools to investigate its secondary metabolites. The results reveal a correlation of chemical diversity and strain phylogeny, with classes of metabolites exclusive to certain phylogroups. We were able to identify previously reported Planomonospora metabolites, including the ureylene-containing oligopeptide antipain, the thiopeptide siomycin including new congeners and the ribosomally synthesized peptides sphaericin and lantibiotic 97518. In addition, we found that Planomonospora strains can produce the siderophore desferrioxamine or a salinichelin-like peptide. Analysis of the genomes of three newly sequenced strains led to the detection of 47 gene cluster families, of which several were connected to products found by LC-MS/MS profiling. This study demonstrates the value of metabolomic studies to investigate poorly explored taxa and provides a first picture of the biosynthetic capabilities of the genus Planomonospora.

microbiology↗