Microbial Natural Products and Biosynthesis

A dLbCas12a-VPR CRISPR activation system works in Aspergillus nidulans, boosting microperfuranone output from the native micA gene and revealing dehydromicroperfuranone as the mic cluster product.

The paper mines over 100,000 genomes to identify 8,500 lanthipeptide precursor peptides, revealing their broader distribution and diversity across bacterial and archaeal phyla.

The paper identifies polyketide biosynthetic gene clusters likely to encode novel antibiotics by analyzing self-resistance genes across genomes.

The paper identifies a new ramoplanin-like biosynthetic gene cluster in Micromonospora chersina and validates its function through CRISPR-Cas9 gene editing, leading to the discovery of the antibiotic chersinamycin.

The paper identifies novel biosynthetic gene clusters in Dothideomycetes fungi and shows their diversity scales with repertoire size, suggesting limited structural redundancy in secondary metabolites.

The paper describes a Penicillium rubens strain with reduced secondary metabolite production, used to efficiently express a polyketide gene cluster for high-yield metabolite production.

This study investigates the evolutionary history and gene structure of the atromentin synthetase gene cluster in fungi, revealing its conservation and convergent evolution across different taxa.

The paper introduces two tools, BiG-SCAPE and CORASON, for analyzing biosynthetic gene clusters in large genomic datasets, demonstrating their utility through validation and discovery of new gene cluster families.

This study investigates the role of the swnR gene in swainsonine biosynthesis in Metarhizium anisopliae by knocking it out and measuring swainsonine levels.

The paper analyzes gene cluster diversity in Fusarium fungi, identifying processes like horizontal transfer and transposable element-driven rearrangements that shape specialized metabolite production.

NeuRiPP improves identification of RiPP precursor peptides by using neural networks trained on diverse datasets, outperforming existing tools in detecting novel RiPP classes.

DDAP predicts biosynthetic pathways of type I PKS by improving module docking domain ordering and affinity prediction, achieving AUC 0.88 and MRR 0.67.

This paper introduces DeepBGC, a deep learning method for improved biosynthetic gene cluster prediction, uncovering previously undetectable clusters with potential novel biological activities.

The paper discovers a new LAP antibiotic, phazolicin, which inhibits bacterial ribosomes in a species-specific manner by blocking the exit tunnel.

This paper describes a method to modify and design non-ribosomal peptide synthetases (NRPSs) using a new fusion point in condensation domains to produce peptides, including non-natural amino acids, at high yields.

The paper develops a pipeline to identify putative resistance genes in biosynthetic gene clusters across fungal genomes, validating it with known resistance genes.

This paper introduces a yeast platform for producing bacterial aromatic polyketides using a synthetic polyketide synthase system.

The paper analyzes biosynthetic gene clusters in cyanobacteria to show that bioactivity of toxins drove their evolutionary diversity and survival strategies.

The paper investigates the role of AbsA2 in antibiotic biosynthesis in Streptomyces coelicolor by analyzing gene expression and DNA-binding sites in a deletion mutant.

EvoMining analyzes enzyme family expansion and recruitment in prokaryotes to identify novel natural product biosynthetic systems and their evolutionary origins.

The paper reports the heterologous reconstitution of hybrid NRPS-PKS assembly lines that generate a combinatorial library of cyclic lipodepsipeptide protease inhibitors through non-standard biosynthetic mechanisms.

This study uses a transcription-factor centric genome mining strategy to discover new RiPP gene clusters in sequenced microorganisms.

This study uses CRISPR/Cas9 to activate a silent gene cluster in Streptomyces sclerotialus, leading to the discovery of scleric acid and its biosynthetic pathway.

The paper uses genomic and metabolomics analyses to study secondary metabolite gene diversification in three Symbiodinium genomes, finding lineage-specific duplications and domain shuffling drive chemical diversity.

A yeast-based refactoring platform (HEx) with new inducible promoters, an engineered host strain, and homology-based assembly expressed 41 cryptic fungal gene clusters; 22 yielded non-native compounds.

The paper identifies secondary metabolite clusters from lake metagenomes using improved binning and analysis tools.

The paper identifies a novel cytochrome P450 enzyme involved in clifednamide biosynthesis and demonstrates its use in engineering Streptomyces strains to produce clifednamides.

clusterTools identifies putative biosynthetic gene clusters by querying functional elements in genomic data.

MetaRiPPquest identifies RiPPs by combining genome/metagenome mining with mass spectrometry analysis, discovering 5 novel natural products from 6 datasets.

This study identifies five types of genetic variation in secondary metabolic gene clusters across 66 strains of Aspergillus fumigatus and links them to evolutionary drivers like mutation, recombination, and horizontal gene transfer.