Kathrin Lang

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

We discovered that E. coli actively imports G-XisoK peptides via the Opp ABC transporter that shuttles small peptides into cells in an ATP-driven manner.
We mapped the uptake mechanism, identified the peptidases removing the N-terminal G and solved the OppA:G-SisoK structure with Michael Groll. 4/9

We spent months designing and synthesizing analogues that wouldn’t be cleaved and be incorporated as G-XisoKs – none worked.
Eventually curiosity won: why were XisoK derivatives incorporated so efficiently, better than any other ncAA? 🤔
That’s when things got exciting 3/9

Building on previous work from our lab on ubiquitin-protein conjugates, we aimed to incorporate G-XisoK ncAAs.
Unexpectedly, the glycine was consistently cleaved off, leaving XisoK efficiently incorporated into proteins via GCE.
A setback at first - we needed G-XisoK modified proteins. 2/9

Hijacking a bacterial ABC transporter for genetic code expansion - Nature Bacterial ATP-binding cassette (ABC) transporters can be utilized and engineered to transport non-canonical amino acids into Escherichia coli for highly efficient synthesis of proteins with novel func...

🚨Our paper is out! 🥳
Hijacking a bacterial ABC transporter for efficient genetic code expansion.
Many congrats to everyone involved - a multi-year effort led by @taruniype.bsky.social @maxfottner.bsky.social
www.nature.com/articles/s41...

it all started years ago with a failed experiment
🧵👇 1/9