Kathrin Lang
@klanglab.bsky.social
Prof for chemical biology at ETH Zurich
Interested in: genetic code expansion - chembio tools - bioorthogonal chemistries - PTMs - Ub in all its shades - protein engineering
Interested in: genetic code expansion - chembio tools - bioorthogonal chemistries - PTMs - Ub in all its shades - protein engineering
Thanks so much Michal! And congrats to your recent story 👏!!
October 22, 2025 at 5:59 PM
Thanks so much Michal! And congrats to your recent story 👏!!
Thanks so much for the nice comment! Much appreciated! 😊
October 22, 2025 at 5:58 PM
Thanks so much for the nice comment! Much appreciated! 😊
Thank you Yogesh! Hope all is well in Dundee!
October 22, 2025 at 5:57 PM
Thank you Yogesh! Hope all is well in Dundee!
😅 many thanks for the nice words!
October 22, 2025 at 5:54 PM
😅 many thanks for the nice words!
Many thanks Tim! 😊
October 17, 2025 at 7:00 AM
Many thanks Tim! 😊
Many thanks Stefan 😊
October 16, 2025 at 9:55 PM
Many thanks Stefan 😊
Thanks André! Congrats to your recent amazing (multi-year) story!
October 16, 2025 at 9:54 PM
Thanks André! Congrats to your recent amazing (multi-year) story!
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
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
October 16, 2025 at 2:06 PM
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
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
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
October 16, 2025 at 2:06 PM
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
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
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
October 16, 2025 at 2:06 PM
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
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
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
October 16, 2025 at 2:06 PM
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
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
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
October 16, 2025 at 2:06 PM
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
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 mapped the uptake mechanism, identified the peptidases removing the N-terminal G and solved the OppA:G-SisoK structure with Michael Groll. 4/9
October 16, 2025 at 2:06 PM
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 mapped the uptake mechanism, identified the peptidases removing the N-terminal G and solved the OppA:G-SisoK structure with Michael Groll. 4/9