ArticlePloS one2013
MIDDAS-M: motif-independent de novo detection of secondary metabolite gene clusters through the integration of genome sequencing and transcriptome data.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed.
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- High-Throughput Mining of Novel Compounds from Known Microbes: A Boost to Natural Product Screening.Molecules (Basel, Switzerland) · 2024Review
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- Characterization of the Biosynthetic Gene Cluster for the Ribosomally Synthesized Cyclic Peptide Epichloëcyclins inJournal of agricultural and food chemistry · 2023Article
- Discovery of L-threonine transaldolases for enhanced biosynthesis of beta-hydroxylated amino acids.Communications biology · 2023Article
- Marine fungi: A treasure trove of novel natural products and for biological discovery.PLoS pathogens · 2023Article
- The Cytotoxic Properties of Extreme Fungi's Bioactive Components-An Updated Metabolic and Omics Overview.Life (Basel, Switzerland) · 2023Review
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- Enhancing chemical and biological diversity by co-cultivation.Frontiers in microbiology · 2023Review
- How to Completely Squeeze a Fungus-Advanced Genome Mining Tools for Novel Bioactive Substances.Pharmaceutics · 2022Review
- Exploring fungal RiPPs from the perspective of chemical ecology.Fungal biology and biotechnology · 2022Review
- Machine learning from Pseudomonas aeruginosa transcriptomes identifies independently modulated sets of genes associated with known transcriptional regulators.Nucleic acids research · 2022Article
- Combatting insects mediated biotic stress through plant associated endophytic entomopathogenic fungi in horticultural crops.Frontiers in plant science · 2022Review
- How to improve the production of peptidyl compounds in filamentous fungi.Frontiers in fungal biology · 2022Article
- Discovery of a gene cluster for the biosynthesis of novel cyclic peptide compound, KK-1, inFrontiers in fungal biology · 2022Article
- Transcriptional Activation of Biosynthetic Gene Clusters in Filamentous Fungi.Frontiers in bioengineering and biotechnology · 2022Review
- The Solvent Dimethyl Sulfoxide Affects Physiology, Transcriptome and Secondary Metabolism ofJournal of fungi (Basel, Switzerland) · 2021Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many bioactive natural products are produced as "secondary metabolites" by plants, bacteria, and fungi. During the middle of the 20th century, several secondary metabolites from fungi revolutionized the pharmaceutical industry, for example, penicillin, lovastatin, and cyclosporine. They are generally biosynthesized by enzymes encoded by clusters of coordinately regulated genes, and several motif-based methods have been developed to detect secondary metabolite biosynthetic (SMB) gene clusters using the sequence information of typical SMB core genes such as polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). However, no detection method exists for SMB gene clusters that are functional and do not include core SMB genes at present. To advance the exploration of SMB gene clusters, especially those without known core genes, we developed MIDDAS-M, a motif-independent de novodetection algorithm for SMB gene clusters. We integrated virtual gene cluster generation in an annotated genome sequence with highly sensitive scoring of the cooperative transcriptional regulation of cluster member genes. MIDDAS-M accurately predicted 38 SMB gene clusters that have been experimentally confirmed and/or predicted by other motif-based methods in 3 fungal strains. MIDDAS-M further identified a new SMB gene cluster for ustiloxin B, which was experimentally validated. Sequence analysis of the cluster genes indicated a novel mechanism for peptide biosynthesis independent of NRPS. Because it is fully computational and independent of empirical knowledge about SMB core genes, MIDDAS-M allows a large-scale, comprehensive analysis of SMB gene clusters, including those with novel biosynthetic mechanisms that do not contain any functionally characterized genes.
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