Also provided
🧬 Complete set of .gb plasmid maps. SI Table 1 describes which plasmids were used to create every subfigure, and which can be obtained from addgene
🖼️ Complete set of .ai figure files. Hopefully sharing these saves someone from re-making cartoons from scratch yet again. 🙏
Also Note: Justin is applying to grad schools as we speak, and is looking to start a PhD next fall somewhere in Europe. If you’re interested in having an absolutely amazing student join your lab, reach out to him! justinbrbooth [at] gmail
Huge congrats to Andre and Justin for getting this project over the finish line! I’m looking forward to sharing this and a few other manuscripts from my former academic lab as they work their way through the writing process 🙂
We used this evolved enzyme to produce halogenated antimicrobial peptides with fermentation at 5L scale. The biosynthesized peptides are just as effective as equivalent peptides produced using expensive chemical methods.
Our evolved RebHEvo4 is a 12-mutant of the wildtype sequence and is >30x more active on a variety of substrates.
It is also MUCH easier to use in vivo thanks to being quite soluble!
Using this circuit, we did 500+ hours of Phage Assisted Continuous Evolution.
(Why no PRANCE? This project happened so early in London that the robot wasn’t even delivered + installed + working smoothly before the continuous flow happened 🤣 🤖)
Note: AARSs are designed to be *really* good at distinguishing between different versions of side chains. That’s their superpower.
Repurposing AARSs for enzyme evolution is a very cool idea, and might work better than using a transcription factor or riboswitch for detecting many small molecules.
Enzymes tend to be difficult to tackle with continuous evolution. The small molecule substrates are slippery and it’s tough to make good gene circuits.
We played a cute trick: we made a circuit that uses an Aminoacyl tRNA Synthetase (AARS) to detect the halogenated product of the enzyme.
Our project focused on engineering enzymes that allow us to add halogens to molecules without those problems.
To fix this problem, we got out the big guns - continuous evolution. We made a PACE circuit that allows us to evolve halogenases in vivo.
Halogenated compounds aren’t well recognized by degradation machinery of the cell, making them more stable. As a result, a fourth of all drugs are halogenated! 💊
BUT
Halogenation is a pain to do with normal chemistry. It’s not stereoselective, and can require quite toxic or expensive chemicals.
What’s ‘halogenated’?
It’s anything with fluorine/chlorine etc from over on the right of the period table. Often halogenated compounds have a hydrogen swapped for, say, a fluorine. They all need one more electron, and so can stand in for one another.
Happy to announce a new preprint from my former academic lab, where we use PACE to evolve halogenase enzymes!
Congrats to Andre Pulschen and Justin Booth who led the study!
🧫 Meet the keynote speakers for the 2025 scverse conference!
Erika Alden DeBenedictis, Co-founder of The Align Foundation & CEO of Pioneer Labs
@erika-alden.bsky.social
@alignbio.bsky.social
@pioneerlabs.bsky.social
#scverse #scverse2025 #StructuralBiology #Biotech #Stanford
📣 Evolutionary Scale is supporting the 2025 Protein Engineering Tournament!
Teams get sponsored ESM inference through
@evolutionaryscale.bsky.social's API (Forge), bringing frontier protein AI models into the competition.
Level playing field, real experiments, open results. Register now 👇
By this time next year, either:
🏆 we'll have engineered PETase enzymes actually work industrially & recycle plastic
... or we'll know that AI-for-proteins is still a bit underbaked 😜
Excited to see what happens!!!! 😬
Spread the word ⬇️
Without a magnetic field, Mars 'leaks' atmosphere to space. But it does so VERY slowly. It would take about 10 Starships a year to 'top up' the atmosphere. So that's a straightforward way to stabilize atmospheric pressure without new tech dev.
We’re lucky to be a nonprofit supported by the @asterainstitute.bsky.social and get to do open science - rapidly sharing all our research and data. Follow along here: pioneerlabs.substack.com
My team at @pioneerlabs.bsky.social is working on making the first life that will live on Mars and form the base of the ecosystem.
If we terraform Mars, it would be a powerful example of human civilization having a net *positive* impact on the surrounding environment.
Research on terraforming would drive advances in climate models, space infrastructure, and biological engineering.
Mars could be green in MY lifetime.
With new tech we could:
[Decades] Warm Mars enough to permit outdoor plant growth 🌞
[Decades] Cultivate a global biosphere 🌱
[Centuries] Allow plants to breathe oxygen into the atmosphere for human life. (Just like they did on Earth!) 🌳
Today I and 11 other scientists describe in Nature Astronomy how recent breakthroughs in launch capabilities, climate, and synthetic biology demand a new assessment of the feasibility of terraforming Mars.
www.erikadebenedictis.com/s/The-case-f...
Heads up: terraforming Mars isn’t just sci-fi, it’s a real possibility that’s possible with today’s technology.
Mars could be green in MY lifetime. 🚀 🌼
What’s stopping us? We need a lot more real research into how to do it right. Don’t nuke Mars!
👇
I went to the 2025 Symposium on Biomaterials, Fuels and Chemicals with an invitation from @nils-averesch.bsky.social to speak about our work at @pioneerlabs.bsky.social engineering organisms for sustainable biomanufacturing on Mars! I took 80 pages of notes. docs.google.com/document/d/1...
Can we do BETTER than evolution with the help of AI? It starts with data. 🧬 🔢
Check out @pioneerlabs.bsky.social's breakdown of how we get large-scale, high-fidelity data out of every engineering and evolution experiment!
This proposal is really interesting. Can you measure enzyme kinetics by adjusting substrate concentration *inside* the cell?
On one hand, cells are noisy. On the other, enzymes behave differently in vitro & in vivo. Best to measure in the conditions you care about!
Very excited by all the execution that's happening at Align! 💪
You know me, I just want to be drowning in data 😛
Time for a LOT of microbe data! 📊 🦠 🤖
@alignbio.bsky.social is aiming to gather a core dataset composed of phenotypes for 1000 diverse microbes cultivated in 1000 diverse conditions.
This labeled data has the potential to take our ability to predict how microbes will behave to the next level!
Align is recruiting for a Data Engineer, and also for a fully-NOT-federally funded Postdoc in the DC area
alignbio.org/careers
