Huge congratulations to Pascal, who led this work during his PhD at ETH Zürich, and to Anh, who started with the idea years ago at TU Munich.
🥼🧪🧫🎉🤩

Why this matters:

Lysine acylations (acetylation, succinylation, etc.) regulate
protein activity, stability and cellular signaling, but accessing homogeneously modified proteins is challenging.

Our approach enables modular installation of diverse lysine acylations at defined sites.

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The concept:
• GCE installs a reactive handle at a defined site in a protein
• A chemoselective amide bond forming reaction then attaches the desired acyl group

➡️ site-specific protein modification
➡️ compatible with complex/folded proteins
➡️ forms the native amide linkage of lysine acylations

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A modular genetic code expansion approach to site-specific lysine acylations A modular strategy combining genetic code expansion with a selective amide bond-forming reaction enables the site-specific installation of lysine acylations on folded proteins. Acylboronates react sel...

🚨 Our new paper is out! 🙌

Bioorthogonal reactions often create bulky, non-native linkages-great for labeling, but not ideal for installing natural PTMs.
We combine GCE with a chemoselective amide-bond forming reaction to install site-specific acylation PTMs.
www.cell.com/chem/fulltex...
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Are you interested in cutting edge #Biochemistry and #ChemBio?

Check out our #Biochemistry2026 meeting in Würzburg from March 16th to 18th.

Deadlines for reduced early bird registration fee and abstracts have been extended to January 28th.

veranstaltungen.gdch.de/microsite/in...

Congrats!! 👏

📢 Open Call! The Max Perutz Labs invite applications for a Full Professorship in Integrative Structure Biology with a focus on in situ structural biology using cryo-electron tomography (cryo-ET) and related methods. More details ➡️ tinyurl.com/brswbymu

How selective is your favourite electrophile? 🤔 🧪 🧫 🎯
Check out this thorough study from the @stephanhacker2.bsky.social lab, now published in Nature Chemistry!
Many congrats to everyone. We are thrilled to have contributed a little! Many congrats to @klanglab.bsky.social alumni Kristina and Marko!

Thanks so much Michal! And congrats to your recent story 👏!!

Thanks so much for the nice comment! Much appreciated! 😊

Thank you Yogesh! Hope all is well in Dundee!

Thanks Felix !

😅 many thanks for the nice words!

Thanks Jim!

Thank you!

Thanks Yael! 😊

Thank you!

Many thanks Tim! 😊

Thanks Marcin!

Thank you Leo!

Thanks Julian!

Many thanks Stefan 😊

Thanks André! Congrats to your recent amazing (multi-year) story!

Thank you Matt!

Super proud of this story! ☺️ Huge thanks to @taruniype.bsky.social for the amazing work - and to @klanglab.bsky.social for the constant support! The first time we saw that phenomenon actually goes all the way back to my Master’s thesis in 2016 🫣 Every now and then, persistence pays off 🤞

In short:
What began as a confusing cleavage artifact became a strategy for programmable import of synthetic building blocks and efficient GCE.
It’s a whole new layer of control over ncAA encoding.
Curiosity turned a failed experiment into a new principle! Very proud of the whole team’s work 🙌 9/9

Next, we asked if the system can be generalized.
By varying the N-terminal residue, we created Z-XisoK tripeptides and evolved transporters for otherwise impermeable Z ncAAs, using GCE as readout for their delivery!
Z-XisoKs even enable co-delivery and co-encoding of two distinct ncAAs! 8/9

However, in nutrient-rich media (like 2-YT), uptake was less efficient – tryptic peptides present in such media competed for OppA binding.
So we evolved OppA to prefer our substrates.
Through FACS screening, we found OppA-iso and made the E. coli strain IsoK12, which thrives in complex media 💪 7/9

With this insight, we built a G-XisoK toolbox.
These tripeptides act as trojan horses 🐴, importing high levels of XisoK into cells.
This enables efficient encoding of bioorthogonal, photocrosslinking, and PTM-mimicking ncAAs – all at wild-type expression levels! 6/9

This revealed how the transporter recognizes and delivers our substrates.
What started as ‘unwanted cleavage’ turned into a transport system we could hijack.
Opp imports G-XisoKs, peptidases remove G, accumulating high concentrations of XisoKs for efficient incorporation via aaRS/tRNA pairs. 5/9