Marnix H Medema

Marnix H Medema
Wageningen University & Research | WUR · Department of Bioinformatics

PhD

About

182
Publications
74,009
Reads
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16,515
Citations
Additional affiliations
December 2021 - present
Wageningen University & Research
Position
  • Professor (Associate)
March 2015 - November 2021
Wageningen University & Research
Position
  • Professor (Assistant)
August 2013 - February 2015
Max Planck Institute for Marine Microbiology
Position
  • PostDoc Position
Education
September 2006 - August 2008
University of Groningen
Field of study
  • Biomolecular Sciences
September 2003 - August 2006
Radboud University
Field of study
  • Biology

Publications

Publications (182)
Article
Full-text available
Many bacteria use small-molecule chelators called metallophores to acquire trace metals from their environment. These molecules play a central role in interactions between bacteria, plants, and animals. Hence, knowing their full diversity is key to combatting infectious diseases as well as harnessing beneficial microbial communities. Metallophore d...
Article
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Covering: up to 2022With the emergence of large amounts of omics data, computational approaches for the identification of plant natural product biosynthetic pathways and their genetic regulation have become increasingly important. While genomes provide clues regarding functional associations between genes based on gene clustering, metabolome mining...
Article
Full-text available
ABSTRACT Marine sponges and their microbial symbiotic communities are rich sources of diverse natural products (NPs) that often display biological activity, yet little is known about the global distribution of NPs and the symbionts that produce them. Since the majority of sponge symbionts remain uncultured, it is a challenge to characterize their N...
Article
Full-text available
Microbiomes play a pivotal role in plant growth and health, but the genetic factors involved in microbiome assembly remain largely elusive. Here, we map the molecular features of the rhizosphere microbiome as quantitative traits of a diverse hybrid population of wild and domesticated tomato. Gene content analysis of prioritized tomato quantitative...
Article
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As efforts to computationally describe and simulate the biochemical world become more commonplace, computer programs that are capable of in silico chemistry play an increasingly important role in biochemical research. While such programs exist, they are often dependency-heavy, difficult to navigate, or not written in Python, the programming languag...
Article
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Strigolactones (SLs) are rhizosphere signaling molecules and phytohormones. The biosynthetic pathway of SLs in tomato has been partially elucidated, but the structural diversity in tomato SLs predicts that additional biosynthetic steps are required. Here, root RNAseq data and co-expression analysis were used for SL biosynthetic gene discovery. Thi...
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Microbial communities might include distinct lineages of closely related organisms that complicate metagenomic assembly and prevent the generation of complete metagenome-assembled genomes (MAGs). Here we show that deep sequencing using long (HiFi) reads combined with Hi-C binning can address this challenge even for complex microbial communities. Us...
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Bacterial specialized metabolites are a proven source of antibiotics and cancer therapies, but whether we have sampled all the secondary metabolite chemical diversity of cultivated bacteria is not known. We analysed ~170,000 bacterial genomes and ~47,000 metagenome assembled genomes (MAGs) using a modified BiG-SLiCE and the new clust-o-matic algori...
Article
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Metagenomics has become a prominent technology to study the functional potential of all organisms in a microbial community. Most studies focus on the bacterial content of these communities, while ignoring eukaryotic microbes. Indeed, many metagenomics analysis pipelines silently assume that all contigs in a metagenome are prokaryotic, likely result...
Article
Microbial specialized metabolites play key roles in microbiome interactions, but their biosynthetic pathways are difficult to characterize. In this issue, Patel et al. (2022) describe new technologies for the computer-aided redesign of gene clusters to facilitate heterologous expression across diverse hosts and showcase their utility by identifying...
Preprint
Full-text available
Marine sponges and their microbial symbiotic communities are rich sources of diverse natural products (NPs) that often display biological activity, yet little is known about their global distribution landscape and the symbionts that produce them. As the majority of sponge symbionts remain uncultured, it is a challenge to characterize their NP biosy...
Article
Full-text available
Major advances in genome sequencing and large-scale biosynthetic gene cluster (BGC) analysis have prompted an age of natural product discovery driven by genome mining. Still, connecting molecules to their cognate BGCs is a substantial bottleneck for this approach. We have developed a mass-spectrometry-based parallel stable isotope labeling platform...
Preprint
Full-text available
Background It is well-known that the microbiome produces a myriad of specialized metabolites with diverse functions. To better predict their structures and identify their producers, integrative genome and metabolome mining is becoming increasingly popular. Metabologenomic correlation methods facilitate the linking of metabolite mass fragmentation s...
Article
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Many bioactive plant cyclic peptides form side-chain-derived macrocycles. Lyciumins, cyclic plant peptides with tryptophan macrocyclizations, are ribosomal peptides (RiPPs) originating from repetitive core peptide motifs in precursor peptides with plant-specific BURP (BNM2, USP, RD22 and PG1beta) domains, but the biosynthetic mechanism for their fo...
Preprint
Full-text available
Microbiomes play a pivotal role in plant growth and health, but the genetic factors involved in microbiome assembly remain largely elusive. Here, 16S amplicon and metagenomic features of the rhizosphere microbiome were mapped as quantitative traits of a recombinant inbred line population of a cross between wild and domesticated tomato. Gene content...
Preprint
Full-text available
A grand challenge in microbial ecology is disentangling the traits of individual populations within complex communities. Various cultivation-independent approaches have been used to infer traits based on the presence of marker genes. However, marker genes are not linked to traits with complete fidelity, nor do they capture important attributes, suc...
Preprint
Full-text available
Metagenomics has become a prominent technology to study the functional potential of all organisms in a microbial community. Most studies focus on the bacterial content of these communities, while ignoring eukaryotic microbes. Indeed, many metagenomics analysis pipelines silently assume that all contigs in a metagenome are prokaryotic. However, beca...
Article
Full-text available
Systematic, large-scale, studies at the genomic, metabolomic, and functional level have transformed the natural product sciences. Improvements in technology and reduction in cost for obtaining spectroscopic, chromatographic, and genomic data coupled with the creation of readily accessible curated and functionally annotated data sets have altered th...
Article
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p>Microbial gene clusters encoding the biosynthesis of primary and secondary metabolites play key roles in shaping microbial ecosystems and driving microbiome-associated phenotypes. Although effective approaches exist to evaluate the metabolic potential of such bacteria through identification of these metabolic gene clusters in their genomes, no au...
Article
Mycotoxins threaten global food safety, public health and cause huge socioeconomic losses. Early detection is an effective preventive strategy, yet efficient biomarkers for early detection of aflatoxigenic Aspergillus species are lacking. Here, we proposed to use untargeted metabolomics and machine learning to mine biomarkers of aflatoxigenic Asper...
Article
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We report the major conclusions of the online open-access workshop "Computational Applications in Secondary Metabolite Discovery (CAiSMD)" that took place from 08 to 10 March 2021. Invited speakers from academia and industry and about 200 registered participants from five continents (Africa, Asia, Europe, South America, and North America) took part...
Preprint
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Bacterial secondary metabolites have been studied for decades for their usefulness as drugs, such as antibiotics. However, the identification of new structures has been decelerating, in part due to rediscovery of known compounds. Meanwhile, multi-resistant pathogens continue to emerge, urging the need for new antibiotics. It is unclear how much che...
Article
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Motivation Genes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalised as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however existing tools are limited to searching local sequence databases. Tools for remotely searching pub...
Article
An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying in...
Article
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Background Phosphorus (P) is an essential macronutrient for plant growth and development. Upon P shortage, plant responds with massive reprogramming of transcription, the Phosphate Starvation Response (PSR). In parallel, the production of strigolactones (SLs)—a class of plant hormones that regulates plant development and rhizosphere signaling molec...
Article
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Soil-borne plant-pathogenic fungi continue to be a major threat to agriculture and horticulture. The genus Fusarium
Article
All organisms produce specialized organic molecules, ranging from small volatile chemicals to large gene-encoded peptides, that have evolved to provide them with diverse cellular and ecological functions. As natural products, they are broadly applied in medicine, agriculture and nutrition. The rapid accumulation of genomic information has revealed...
Article
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Ribosomally synthesized and post-translationally modified peptides (RiPPs) form a highly diverse class of natural products, with various biotechnologically and clinically relevant activities. A recent increase in discoveries of novel RiPP classes suggests that currently known RiPPs constitute just the tip of the iceberg. Genome mining has been a dr...
Article
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Anaerobic bacteria from the human microbiome produce a wide array of molecules at high concentrations that can directly or indirectly affect the host. The production of these molecules, mostly derived from their primary metabolism, is frequently encoded in metabolic gene clusters (MGCs). However, despite the importance of microbiome-derived primary...
Article
Full-text available
Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows to discover novel natural products. Since 2011, the "antibiotics and secondary metabolite analysis shell—antiSMASH" (https://antismash.secondarymetabolites.org/) has...
Preprint
Full-text available
Microbial communities in many environments include distinct lineages of closely related organisms which have proved challenging to separate in metagenomic assembly, preventing generation of complete metagenome-assembled genomes (MAGs). The advent of long and accurate HiFi reads presents a possible means to address this challenge by generating compl...
Article
Full-text available
Trans-acyltransferase polyketide synthases (trans-AT PKSs) are bacterial multimodular enzymes that biosynthesize diverse pharmaceutically and ecologically important polyketides. A notable feature of this natural product class is the existence of chemical hybrids that combine core moieties from different polyketide structures. To understand the prev...
Article
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Surfactin is a lipoheptapeptide produced by several Bacillus species and identified for the first time in 1969. At first, the biosynthesis of this remarkable biosurfactant was described in this review. The peptide moiety of the surfactin is synthesized using huge multienzymatic proteins called NonRibosomal Peptide Synthetases. This mechanism is res...
Preprint
Full-text available
The gut microbiota produce hundreds of small molecules, many of which modulate host physiology. Although efforts have been made to identify biosynthetic genes for secondary metabolites, the chemical output of the gut microbiome consists predominantly of primary metabolites. Here, we systematically profile primary metabolic genes from the gut microb...
Article
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Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding the identification of natural product biosynthetic origins and metabolite structures.
Preprint
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Microbial community analysis of aquatic environments showed that an important component of microbial diversity consists of bacteria with cell sizes smaller than ~0.1 μm. However, so far no study investigated if such bacteria with small cell sizes exist in terrestrial environments as well. Here, we isolated soil bacteria that passed through a 0.1 μm...
Article
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Covering: 2020 Bioinformatic approaches to document and analyse chemical structures, biosynthetic gene clusters and analytical data play an important role in the study of natural products. Every year, such a large number of new algorithms, tools and databases are released, that it is difficult to keep track of all the latest developments. The aim o...
Preprint
Full-text available
Microorganisms produce an immense variety of natural products through the expression of Biosynthetic Gene Clusters (BGCs): physically clustered genes that encode the enzymes of a specialized metabolic pathway. These natural products cover a wide range of chemical classes (e.g., aminoglycosides, lantibiotics, nonribosomal peptides, oligosaccharides,...
Article
Full-text available
Background Genome mining for biosynthetic gene clusters (BGCs) has become an integral part of natural product discovery. The >200,000 microbial genomes now publicly available hold information on abundant novel chemistry. One way to navigate this vast genomic diversity is through comparative analysis of homologous BGCs, which allows identification o...
Article
Full-text available
One of the fundamental tenets of biology is that the phenotype of an organism (Y) is determined by its genotype (G), the environment (E), and their interaction (GE). Quantitative phenotypes can then be modeled as Y = G + E + GE + e, where e is the biological variance. This simple and tractable model has long served as the basis for studies investig...
Preprint
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Around weaning, piglets are susceptible to infection by bacterial pathobionts, leading to increased morbidity and mortality. We identified isolates of Rothia nasisuis in the upper respiratory tract of weaned healthy piglets that produce valinomycin in vitro and in vivo via its vlm -encoded non-ribosomal peptide synthase (NRPS) enzyme complex. Valin...
Article
Full-text available
Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiP...
Preprint
Full-text available
Microbial gene clusters encoding the biosynthesis of primary and secondary metabolites play key roles in shaping microbial ecosystems and driving microbiome-associated phenotypes. Although effective approaches exist to evaluate the metabolic potential of such bacteria through identification of metabolic gene clusters in their genomes, no automated...
Article
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...
Article
Full-text available
Microorganisms produce natural products that are frequently used in the development of antibacterial, antiviral, and anticancer drugs, pesticides, herbicides, or fungicides. In recent years, genome mining has evolved into a prominent method to access this potential. antiSMASH is one of the most popular tools for this task. Here, we present version...
Article
Full-text available
Computational analysis of biosynthetic gene clusters (BGCs) has revolutionized natural product discovery by enabling the rapid investigation of secondary metabolic potential within microbial genome sequences. Grouping homologous BGCs into Gene Cluster Families (GCFs) facilitates mapping their architectural and taxonomic diversity and provides insig...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
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Bioinformatics-powered discovery of novel ribosomal natural products (RiPPs) has historically been hindered by the lack of a common genetic feature across RiPP classes. Herein, we introduce RRE-Finder, a method for identifying RRE domains, which are present in a majority of prokaryotic RiPP biosynthetic gene clusters (BGCs). RRE-Finder identifies R...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Covering: 2010–2020 The digital revolution is driving significant changes in how people store, distribute, and use information. With the advent of new technologies around linked data, machine learning and large-scale network inference, the natural products research field is beginning to embrace real-time sharing and large-scale analysis of digitize...
Article
Full-text available
Enzymes that cleave ATP to activate carboxylic acids play essential roles in primary and secondary metabolism in all domains of life. Class I adenylate-forming enzymes share a conserved structural fold but act on a wide range of substrates to catalyze reactions involved in bioluminescence, nonribosomal peptide biosynthesis, fatty acid activation, a...
Preprint
Full-text available
Background Genome mining for Biosynthetic Gene Clusters (BGCs) has become an integral part of natural product discovery. The >200,000 microbial genomes now publicly available hold information on abundant novel chemistry. One way to navigate this vast genomic diversity is through comparative analysis of homologous BGCs, which allows identification o...
Preprint
Full-text available
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...
Article
Motivation: Polyketide synthases are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by cis-AT modular polyketide synthases (PKSs), which are organized in assembly lines, in which multiple enzymes line up in a spec...
Article
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Bacterial strains of the phylum Planctomycetes occur ubiquitously, but are often found on surfaces of aquatic phototrophs, e.g. alga. Despite slower growth, planctomycetes are not outcompeted by faster-growing bacteria in biofilms on such surfaces; however, strategies allowing them to compensate for slower growth have not yet been investigated. Her...
Article
Actinobacteria constitute a highly diverse bacterial phylum with an unrivalled metabolic versatility. They produce most of the clinically used antibiotics and a plethora of other natural products with medical or agricultural applications. Modern ‘omics’-based technologies have revealed that the genomic potential of Actinobacteria greatly outmatches...
Article
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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 antibio...