Microbial Natural Products and Biosynthesis

Further biochemical profiling of Hypholoma fasciculare metabolome reveals its chemo-genetic diversity

This study profiles the metabolome of Hypholoma fasciculare to identify bioactive compounds and their genetic pathways, revealing its potential as a source of novel antibiotics.

Synthetic Zippers as an Enabling Tool for Engineering of Non-Ribosomal Peptide Synthetases

The paper introduces synthetic zippers to split and recombine NRPS fragments, enabling the production of novel non-ribosomal peptides at high titres.

Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions

The paper introduces NPLinker, a framework that combines scoring functions to link microbial genomic and metabolomic data, improving identification of biosynthetic gene clusters and their associated metabolites.

Accurate de novo identification of biosynthetic gene clusters with GECCO

A linear conditional random field over ordered protein-domain annotations finds biosynthetic gene clusters de novo more precisely than DeepBGC and runs over three times faster on one CPU.

Comparative genome and transcriptome analyses revealing interspecies variations in the expression of fungal biosynthetic gene clusters

The paper compares genome and transcriptome data from five Aspergillus species to analyze variations in biosynthetic gene cluster expression, finding that conserved clusters show diverse expression patterns despite genetic conservation.

Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase

The paper identifies key residues in an acyltransferase that influence substrate selectivity and demonstrates how swapping structural motifs can alter substrate specificity in polyketide synthases.

Biosynthesis and heterologous expression of cacaoidin, the first member of the lanthidin family of RiPPS

The paper identifies and clones the cacaoidin biosynthetic gene cluster from Streptomyces cacaoi CA-170360 and describes its heterologous expression.

Cell-Free Biosynthesis to Evaluate Lasso Peptide Formation and Enzyme-Substrate Tolerance

This study uses cell-free biosynthesis to produce lasso peptides, demonstrating their sequence diversity and enzyme-substrate tolerance.

Phylogenetic distribution of secondary metabolites in the Bacillus subtilis species complex

The paper analyzes the phylogenetic distribution of biosynthetic gene clusters in the Bacillus subtilis group to understand secondary metabolite production patterns and conservation.

Natural combinatorial genetics and prolific polyamine production enable siderophore diversification in Serratia plymuthica

This study identifies multiple siderophores produced by Serratia plymuthica V4 using three gene clusters and a polyamine superpathway, highlighting enterobactin's role in bacterial fitness and the strain's potential for industrial polyamine production.

Transporter genes in biosynthetic gene clusters predict metabolite characteristics and siderophore activity

The paper uses transporter gene frequencies to predict metabolite characteristics and identifies siderophore-like BGCs in gut microbiomes.

The Functional Order (FunOrder) tool - Identification of essential biosynthetic genes through computational molecular co-evolution

The paper introduces FunOrder, a tool that identifies essential biosynthetic genes in BGCs using computational molecular co-evolution, improving upon existing methods that struggle with distinguishing essential genes from gap genes.

Comparative whole-genome analysis of a Thar desert strain Streptomyces sp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

The paper sequenced and analyzed the genome of a desert Streptomyces strain, identifying novel biosynthetic gene clusters and metabolic adaptations to extreme desert conditions.

Mining metagenomes for natural product biosynthetic gene clusters: unlocking new potential with ultrafast techniques

The paper introduces BiG-MEx, an ultrafast tool for mining metagenomic data to identify and analyze biosynthetic gene clusters, demonstrating its effectiveness on TARA Oceans and Human Microbiome Project datasets.

One pathway, two cyclic pentapeptides: heterologous expression of BE-18257 A-C and pentaminomycins A-E from Streptomyces cacaoi CA-170360

The paper demonstrates the heterologous expression of two cyclic pentapeptide families from Streptomyces cacaoi CA-170360, showing their biosynthesis by two nonribosomal peptide synthetases and a Penicillin Binding Protein enzyme.

BiG-SLiCE: A Highly Scalable Tool Maps the Diversity of 1.2 Million Biosynthetic Gene Clusters

BiG-SLiCE clusters 1.2 million biosynthetic gene clusters from microbial genomes and MAGs efficiently, enabling analysis of secondary metabolic diversity and novel chemistry.

Pathway engineering in yeast for synthesizing the complex polyketide bikaverin

This study engineers the biosynthesis of the polyketide bikaverin in yeast by enhancing enzyme expression and using enzyme fusion to increase yield.

An Unconventional Melanin Biosynthetic Pathway in Ustilago maydis

This paper identifies a novel melanin biosynthetic pathway in Ustilago maydis involving multiple polyketide synthases and other enzymes, distinct from known fungal melanin pathways.

Heterologous expression of cryptomaldamide in a cyanobacterial host

This paper develops genetic tools for heterologous expression of biosynthetic gene clusters in cyanobacteria, enabling high-titer production of cryptomaldamide in Anabaena.

Efficient rational modification of non-ribosomal peptides by adenylation domain substitution

The paper demonstrates that substituting adenylation domains in NRPS enzymes can generate novel non-ribosomal peptides, challenging previous assumptions about substrate specificity.

A bimodular PKS platform that expands the biological design space

The paper engineers bimodular PKS systems to produce unnatural polyketides as bio-based chemicals, demonstrating both successes and challenges in product fidelity.

RRE-Finder: A Genome-Mining Tool for Class-Independent RiPP Discovery

RRE-Finder identifies RRE domains across RiPP biosynthetic gene clusters, discovering novel classes and providing a dataset for further biochemical study.

Phylogenomic analyses of non-Dikarya fungi supports horizontal gene transfer driving diversification of secondary metabolism in the amphibian gastrointestinal symbiont, Basidiobolus

The paper identifies SM gene clusters in non-Dikarya fungi, particularly Basidiobolus, and shows horizontal gene transfer contributes to SM diversification in amphibian gut symbionts.

Biosynthesis of alkylcitric acids in Aspergillus niger involves both co-localized and unlinked genes

This study identifies and characterizes the biosynthetic pathway for alkylcitric acids in Aspergillus niger using genomic analysis and experimental overexpression.

Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines

The paper introduces PKSpop, a coevolution-based method to predict protein-protein interactions in PKS assembly lines, achieving 80% accuracy in predicting protein order.

CRISPR-mediated activation of biosynthetic gene clusters for bioactive molecule discovery in filamentous fungi

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.

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

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.

Identification of polyketide biosynthetic gene clusters that harbor self-resistance target genes

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

Targeted Genome Mining Discovery of the Ramoplanin Congener Chersinamycin from the Dynemicin-Producer Micromonospora chersina DSM 44154.

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 architecture of metabolism maximizes biosynthetic diversity in the largest class of fungi

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.