iiinova — where your digital self keeps evolving

Huge credit to @suzannejansen.bsky.social, who led this work. But without Luis Guerra & Manuel Müller from @mueller-lab-kcl.bsky.social, as well as Cristina Duran & @silviaosuna.bsky.social we could have never provided experimental and computational evidence for isoaspartate formation! 🤝 (4/4)

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Substituting this conserved histidine with a non-canonical histidine analog or glutamine can overcome the inhibition! A beautiful example of modern mechanistic enzymology and an important step toward our longer-term goal of making FAcDs fit for PFAS degradation. 🌍 One C-F bond at a time! (3/4)

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We combined kinetic studies, mass spectrometry, biochemical analyses and computational modeling to solve this puzzle. The culprit is unexpected: isomerization of the catalytic aspartate to isoaspartate. Even more exciting, we found a nearby histidine that acts as a gatekeeper for this process. (2/4)

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Substituting a conserved histidine alleviates difluoroacetate-dependent isoaspartate formation in a fluoroacetate dehalogenase

🚨New preprint alert! What a difference one C-F bond can make!🚨 Fluoroacetate dehalogenases (FAcDs) are remarkably good at breaking C-F bonds. But add just ONE more C-F bond to the substrate and suddenly the enzyme is inhibited. So, what’s going on? (1/4) www.biorxiv.org/content/10.6...

biorxiv.org

Organofluorides are ubiquitous in modern society, but their persistence poses significant environmental and health risks. Fluoroacetate dehalogenases (FAcDs) are promising candidates for the bioremedi...

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A huge congratulations to Titia for this outstanding Review! 👏 She did an exceptional job navigating a rapidly growing field, compiling the literature, and providing a thoughtful, critical, and forward-looking perspective on where hybrid peptide discovery is heading.

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We discuss: 🔹 cysteine- and lysine-targeting cyclization strategies 🔹 residue-selective and chemoenzymatic approaches 🔹 proximity-driven chemical transformations 🔹 exploiting the chemical robustness of bacteriophages (4/5)

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What if we could introduce these chemical improvements during the discovery process itself? Our review evaluates strategies to select hybrid macrocyclic peptides by bacteriophage display, which combine the diversity of peptide libraries with synthetic scaffolds (3/5)

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Macrocyclic peptides achieve the target selectivity of biologics while retaining many advantages of small molecules. But discovering great peptide binders is only the beginning. Many candidates require extensive medicinal chemistry optimization to improve: (2/5)

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chemistry-europe.onlinelibrary.wiley.com

New review out in Chemistry – A European Journal! Hybrid macrocyclic peptides: combining biological selection with synthetic chemistry to discover next-generation therapeutics. Why are hybrid macrocyclic peptides so exciting? 👇 (1/5) chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/...

Hybrid Macrocyclic Peptides — Synthetic Strategies to Diversify and Cyclize Peptide Libraries in Phage Display Selections

Hybrid macrocyclic peptides unite genetically encoded peptide libraries with the structural complexity of synthetic small molecules. This Review critically analyzes phage-compatible cyclization and d...

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Clemens @mayerlab.bsky.social · 19/12/2025

📢 📢 📢 !!!Come and join us!! 📢 📢 📢 We are looking for a Postdoctoral Researcher with in-depth experience in next- and third-generation sequencing to help us understand the fitness landscapes of complex biomolecules! Please spread the word :) werkenbij.rug.nl/vacature/pos...

werkenbij.rug.nl

Postdoctoral Researcher – Next-gen sequencing for machine-learning guided directed evolution - Rijksuniversiteit Groningen

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Clemens @mayerlab.bsky.social · 08/10/2025

Is today the day for phosphoramidite chemistry and/or next-gen sequencing??? #nobel #chemistry

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Clemens @mayerlab.bsky.social · 16/09/2025

Was great seeing you again :)

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Reposted by Clemens

Suzanne C. Jansen @suzannejansen.bsky.social · 17/07/2025

Preprint alert! With #PFAS contamination becoming an environmental crisis, we dared to engineer natural defluorinases towards degradation of (un)natural organofluorides. How? Check out our robust growth-based selection platform here: www.biorxiv.org/content/10.1... thanks to @mayerlab.bsky.social !

biorxiv.org

Engineering fluoroacetate dehalogenase by growth-based selections to degrade non-natural organofluorides

The widespread use of organofluorides in modern society has inadvertently led to the bioaccumulation of harmful pollutants, most prominently per- and polyfluorinated alkyl substances (PFAS). In princi...

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Overall, our study presents the first large-scale engineering campaign of FAcDs and introduces an operationally simple selection platform that paves the way toward adapting these enzymes for the sustainable degradation of contaminating organofluorides. (5/5)

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Forcing populations of bacteria expressing tens of thousands of distinct FAcD-variants to utilize various organofluorides as sole carbon source, we elicited a panel of FAcD variants with improved activities and drastically altered substrate profiles. (4/5)

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To expand the substrate scope of FAcDs for non-natural organofluorides, we designed and applied a robust growth-based selection, in which the FAcD-catalyzed C—F bond cleavage of synthetic organofluorides generates metabolizable C-sources. (3/5)

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