MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

The bZIP transcription factor BIP1 of the rice blast fungus is essential for infection and regulates a specific set of appressorium genes.

The rice blast fungus Magnaporthe oryzae differentiates specialized cells called appressoria that are required for fungal penetration into host leaves. In this study, we identified the novel basic leucine zipper (bZIP) transcription factor BIP1 (B-ZIP Involved in Pathogenesis-1) that is essential for pathogenicity. BIP1 is required for the infection of plant leaves, even if they are wounded, but not for appressorium-mediated penetration of artificial cellophane membranes.

Detection and quantification of the histone code in the fungal genus Aspergillus.

In eukaryotes, the combination of different histone post-translational modifications (PTMs) - the histone code - impacts the chromatin organization as compact and transcriptionally silent heterochromatin or accessible and transcriptionally active euchromatin. Although specific histone PTMs have been studied in fungi, an overview of histone PTMs and their relative abundance is still lacking. Here, we used mass spectrometry to detect and quantify histone PTMs in three fungal species belonging to three distinct taxonomic sections of the genus Aspergillus (Aspergillus niger, Aspergillus nidulans (two strains), and Aspergillus fumigatus).

Evolutionary relationships of adenylation domains in fungi.

Non-ribosomal peptide synthetases (NRPSs) and NRPS-like enzymes are abundant in microbes as they are involved in the production of primary and secondary metabolites. In contrast to the well-studied NRPSs, known to produce non-ribosomal peptides, NRPS-like enzymes exhibit more diverse activities and their evolutionary relationships are unclear. Here, we present the first in-depth phylogenetic analysis of fungal NRPS-like A domains from functionally characterized pathways, and their relationships to characterized A domains found in fungal NRPSs.

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC.

The histone code of the fungal genus uncovered by evolutionary and proteomic analyses.

Chemical modifications of DNA and histone proteins impact the organization of chromatin within the nucleus. Changes in these modifications, catalysed by different chromatin-modifying enzymes, influence chromatin organization, which in turn is thought to impact the spatial and temporal regulation of gene expression. While combinations of different histone modifications, the histone code, have been studied in several model species, we know very little about histone modifications in the fungal genus , whose members are generally well studied due to their importance as models in cell and molecular biology as well as their medical and biotechnological relevance.

A genomic journey in the secondary metabolite diversity of fungal plant and insect pathogens: from functional to population genomics.

Fungal pathogens produce a broad array of secondary metabolites (SMs), which allow the fungus to thrive in its natural habitat and gain competitive advantage. Analysis of the genetically encoded blueprints for SM assembly highlighted that only a small portion of the SMs these fungi are capable of producing are known, and even fewer have been investigated for their natural function. Using molecular tools, a lot of progress has been made recently in identifying the blueprint products and linking them to their ecological purpose such as the peptide virulence factor fusaoctaxin A released by Fusarium graminearum during infection of wheat or the F.

Evolution-Informed Discovery of the Naphthalenone Biosynthetic Pathway in Fungi.

Fungi produce a wide diversity of secondary metabolites with interesting biological activities for the health, industrial, and agricultural sectors. While fungal genomes have revealed an unexpectedly high number of biosynthetic pathways that far exceeds the number of known molecules, accessing and characterizing this hidden diversity remain highly challenging. Here, we applied a combined phylogenetic dereplication and comparative genomics strategy to explore eight lichenizing fungi.

Characterization of NRPS and PKS genes involved in the biosynthesis of SMs in Alternaria dauci including the phytotoxic polyketide aldaulactone.

Alternaria dauci is a Dothideomycete fungus, causal agent of carrot leaf blight. As a member of the Alternaria genus, known to produce a lot of secondary metabolite toxins, A. dauci is also supposed to synthetize host specific and non-host specific toxins playing a crucial role in pathogenicity.

A Bioinformatics Workflow for Investigating Fungal Biosynthetic Gene Clusters.

Predicting secondary metabolite biosynthetic gene clusters is a routine analysis performed for each newly sequenced fungal genome. Yet, the usefulness of such predictions remains restricted as they provide total numbers of biosynthetic pathways with only very limited biological significance. In this chapter, we describe a workflow to predict and analyze biosynthetic gene clusters in fungal genomes.

Hybridizations Between of Pave the Way for a New Biocontrol Strategy to Manage Fungal Plant Pathogens.

Hybridization and adaptation to new hosts are important mechanisms of fungal disease emergence. Evaluating the risk of emergence of hybrids with enhanced virulence is then key to develop sustainable crop disease management. We evaluated this risk in , the fungus responsible for the common and serious scab disease on Rosaceae hosts, including apple, pyracantha, and loquat.

Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity.

Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number of biosynthetic gene clusters (BGCs) in fungi is much larger than expected. Unfortunately, most of them are silent or barely expressed under laboratory culture conditions.

Evolutionary Histories of Type III Polyketide Synthases in Fungi.

Type III polyketide synthases (PKSs) produce secondary metabolites with diverse biological activities, including antimicrobials. While they have been extensively studied in plants and bacteria, only a handful of type III PKSs from fungi has been characterized in the last 15 years. The exploitation of fungal type III PKSs to produce novel bioactive compounds requires understanding the diversity of these enzymes, as well as of their biosynthetic pathways.

The High-Quality Complete Genome Sequence of the Opportunistic Fungal Pathogen Candida vulturna CBS 14366.

Candida vulturna is a new member of the Candida haemulonii species complex that recently received much attention as it includes the emerging multidrug-resistant pathogen Candida auris. Here, we describe the high-quality genome sequence of C. vulturna type strain CBS 14366 to cover all genomes of pathogenic C.

MIBiG 2.0: a repository for biosynthetic gene clusters of known function.

Fueled by the explosion of (meta)genomic data, genome mining of specialized metabolites has become a major technology for drug discovery and studying microbiome ecology. In these efforts, computational tools like antiSMASH have played a central role through the analysis of Biosynthetic Gene Clusters (BGCs). Thousands of candidate BGCs from microbial genomes have been identified and stored in public databases.

Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete?

Fungal secondary metabolites are small molecules that exhibit diverse biological activities exploited in medicine, industry and agriculture. Their biosynthesis is governed by co-expressed genes that often co-localize in gene clusters. Most of these secondary metabolite gene clusters are inactive under laboratory conditions, which is due to a tight transcriptional regulation.

Population Genome Sequencing of the Scab Fungal Species , , and .

The genus comprises fungal species that are pathogens on host plants, including and on apple, on sorbus and on pear. Although the genetic structure of populations has been investigated in detail, genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87 strains that represent each species and each population within We present a PacBio genome assembly for the EU-B04 reference isolate.

Draft Genome Sequence of the Wood-Staining Ascomycete DSM 107184.

DSM 107184 is a wood-decomposing ascomycetous fungus known to produce the bluish-green dimeric naphthoquinone derivate xylindein. Here, we present the first draft genome sequence, which contains 588 contigs with a total length of 33.1 Mb.

Nonproteinaceous effectors: the terra incognita of plant-fungal interactions.

Molecular plant-fungal interaction studies have mainly focused on small secreted protein effectors. However, accumulating evidence shows that numerous fungal secondary metabolites are produced at all stages of plant colonization, especially during early asymptomatic/biotrophic phases. The discovery of fungal small RNAs targeting plant transcripts has expanded the fungal repertoire of nonproteinaceous effectors even further.

Assignment of a dubious gene cluster to melanin biosynthesis in the tomato fungal pathogen Cladosporium fulvum.

Pigments and phytotoxins are crucial for the survival and spread of plant pathogenic fungi. The genome of the tomato biotrophic fungal pathogen Cladosporium fulvum contains a predicted gene cluster (CfPKS1, CfPRF1, CfRDT1 and CfTSF1) that is syntenic with the characterized elsinochrome toxin gene cluster in the citrus pathogen Elsinoë fawcettii. However, a previous phylogenetic analysis suggested that CfPks1 might instead be involved in pigment production.

Specific Hypersensitive Response-Associated Recognition of New Apoplastic Effectors from Cladosporium fulvum in Wild Tomato.

Tomato leaf mold disease is caused by the biotrophic fungus Cladosporium fulvum. During infection, C. fulvum produces extracellular small secreted protein (SSP) effectors that function to promote colonization of the leaf apoplast.

Down-regulation of cladofulvin biosynthesis is required for biotrophic growth of Cladosporium fulvum on tomato.

Fungal biotrophy is associated with a reduced capacity to produce potentially toxic secondary metabolites (SMs). Yet, the genome of the biotrophic plant pathogen Cladosporium fulvum contains many SM biosynthetic gene clusters, with several related to toxin production. These gene clusters are, however, poorly expressed during the colonization of tomato.

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization.

Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps.