Wilfred A. van der Donk

This study maps the sequence preferences of the generalist class II lanthipeptide synthetase ProcM using mRNA display and machine learning, revealing moderate predictive accuracy compared to specialized enzymes.

The paper investigates the mechanism of peptide modifications by DybH and ChrH enzymes, identifying key steps in macrocyclization and heterocycle formation through mutational analysis.

This study shows that LanCL proteins are essential for muscle regeneration in aging mice, as their loss impairs regeneration and increases inflammation.

This paper identifies the final steps in fosfazinomycin biosynthesis, revealing an unexpected use of RiPP machinery to assemble phosphonate and hydrazine moieties.

The P450 ApyO crosslinks a 10-residue C-terminal peptide, and substitutions in the YLY motif switch the linkage among C−C, N−C and C−O bonds.

The paper identifies CoiH as an enzyme that catalyzes the formation of a sulfoxide group in methyllanthionine of anti-phage lanthipeptides.

This paper identifies and characterizes the sinefungin biosynthetic gene cluster, revealing unconventional biocatalytic strategies involving a B12-dependent radical SAM enzyme and PEARLs for nucleoside modification.

The paper identifies and structurally analyzes two class II lanthipeptides from a thermophilic bacterium, revealing deviations in thioether ring formation and demonstrating antimicrobial activity.

The paper identifies and characterizes a RiPP biosynthetic gene cluster that introduces nitrile groups via an AS-like enzyme, expanding knowledge of RiPP structural diversity and enzymatic versatility.

The paper presents the first high-resolution structure of two interacting lanthipeptides and shows how they disrupt cell membranes.

This study identifies a new phosphonate antibiotic, flavophos, produced by Burkholderia, which inhibits lumazine synthase and confers resistance when expressed in E. coli.

This study determines the structure, biosynthesis, and bioactivity of nostolysamides, a class II lanthipeptide from Nostoc punctiforme, showing antibacterial and antifungal activity through membrane disruption.

The paper identifies a new class of lipidated RiPPs that use the bacterial lipoprotein pathway for maturation, showing structural diversity and widespread distribution across bacterial phyla.

This study determines the unique ring pattern of the Rosβ lanthipeptide of roseocin using NMR spectroscopy and Marfeys analysis.

This study identifies two HEXXH enzymes that catalyze oxidative backbone cleavage in RiPP biosynthesis by recognizing specific peptide motifs.

This paper identifies the biosynthetic pathway for ammosamide C, revealing novel enzymatic steps and roles for PEARLs beyond traditional PTMs.

This study investigates the substrate specificity of the PEARL BhaBCAla, showing it can use non-cognate amino acids and tRNAs for peptide extension, with efficiency depending on both amino acid and tRNA features.

This paper identifies a new heme enzyme family that catalyzes hydrazine formation in natural product biosynthesis through a four-electron reduction of nitrite.

This study characterizes thermoglycocin, a novel glycocin from Thermoanaerobacterium thermosaccharolyticum, with three disulfide bonds, O- and S-GlcNAcylation, and a unique C39 protease cleavage site.

This study identifies a conserved FHAFRF-motif in precursor peptides of MNIO-encoding BGCs and demonstrates that MNIO and B12-rSAM enzymes catalyze ortho-hydroxylation and crosslinking of phenylalanine residues to form macrocyclic peptides.

This study uses kinetic assays to show that reaction rates of isolated modifications can predict the final ring pattern but not the order of modification in ProcM variants.

The paper reports an expression system for producing lanthipeptides and cytolysin L derivatives in mammalian cells and demonstrates their nuclear targeting.

This study identifies a lantibiotic dehydratase that catalyzes peptide bond formation in the opposite direction of NRPS and PKS biosynthesis, revealing its role as a separate amide bond-forming machinery.

This study reveals the complexity of pyrroloiminoquinone biosynthesis by identifying four additional enzymes that correct a previously proposed pathway and show that amino groups come from glycine, asparagine, and leucine.

This study discovers a new class of macrocyclic peptides by mining genomes for biosynthetic gene clusters, revealing novel enzymatic modifications involving a cytochrome P450 and other enzymes.

The paper characterizes six gut-derived nisin-like lantibiotics, evaluates their antimicrobial activity against pathogens and commensals, and identifies key residues affecting their activity.

This study develops a simple method to determine lanthipeptide stereochemistry using Marfeys analysis with low sample requirements and standard equipment.

This paper identifies bibacillin 1, a two-component lantibiotic from Bacillus thuringiensis, showing cooperative bactericidal activity and distinct mechanism of action compared to other lantibiotics.

This study shows that lantibiotic resistance genes in gut bacteria affect microbiota composition and function, with implications for microbiome health and resistance strategies.

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.