Ashty Karim

Chemical Engineer | Synthetic Biologist | Assist. Professor | moved to LinkedIn

[Ashty Karim @akarimlab]

Out now our work to accelerate the development of biocatalysts completely outside of cells! Barely using twitter, and now engaging more frequently on LinkedIn: https://t.co/bZYs1PV1DR

[Michael C. Jewett @MichaelCJewett]

How can we create versatile biocatalysts for sustainable chemistry faster? We can use ML-guided design of enzymes enabled by synthetic biology. Research led by Grant Landwehr & Jon Bogart @NUSynBio @akarimlab

https://t.co/w5LhjzrsqL

[Kevin K. Yang 楊凱筌 @KevinKaichuang]

An ML-guided, cell-free enzyme engineering platform for optimizing substrate preference.

@akarimlab @MichaelCJewett

[Biology+AI Daily @BiologyAIDaily]

Accelerated enzyme engineering by machine-learning guided cell-free expression @NatureComms

1. This study presents a novel machine-learning (ML)-guided platform for enzyme engineering, integrating cell-free DNA assembly, expression, and functional assays. It significantly accelerates the process by exploring protein sequence space and optimizing enzymes for diverse chemical reactions.

2. The platform was demonstrated on amide synthetases, evaluating 1217 enzyme variants across 10,953 reactions. Using ML, researchers built predictive models that achieved up to 42-fold activity improvements over parent enzymes for nine pharmaceutical compounds.

3. A key innovation is the use of cell-free gene expression systems in a design-build-test-learn (DBTL) workflow, which bypasses the limitations of traditional directed evolution, such as narrow sequence-space exploration and iterative site saturation mutagenesis.

4. The ML-guided framework includes augmented ridge regression models, which use sequence-function relationship data to predict higher-order mutants. These models showed superior performance, requiring only CPU-level computational resources.

5. This approach enabled rapid creation of specialized biocatalysts, reducing enzyme engineering timelines to just one week for multiple campaigns. For example, a quadruple mutant for moclobemide synthesis achieved a 96% conversion rate with a 42-fold increase in catalytic efficiency.

6. Beyond activity improvements, the engineered enzymes retained strict regio- and stereoselectivity without additional selective pressures, showcasing the robustness of the framework.

7. The study emphasizes the versatility of the platform, applying it to engineer six additional pharmaceutical compounds, yielding activity improvements ranging from 1.6- to 34-fold over the wild type.

8. By combining ML with cell-free systems, the framework circumvents path dependencies and expands the protein engineering toolbox, enabling simultaneous exploration of broad sequence spaces with reduced experimental burden.

@MichaelCJewett @akarimlab
💻Code: https://t.co/XQkigw2Wfj
📜Paper: https://t.co/gM5saNk5T2
#MachineLearning #ProteinEngineering #SyntheticBiology #Biocatalysis

[Michael C. Jewett @MichaelCJewett]

What is needed to accelerate enzyme engineering using machine learning? #Data We develop a ML-guided platform that integrates DNA assembly, gene expression, and functional assays. ML models predict improved variants. @akarimlab @NUSynBio @NatureComms

https://t.co/BmlojOIK4A

[Michael C. Jewett @MichaelCJewett]

Engineered enzymes can advance green chemistry. Unfortunately, engineering enzymes remains hard. In @NatureComms, we showed that AI-guided design coupled to cell-free systems can predict mutants as well as lab experiments. @akarimlab

https://t.co/8czWQPThDn

[Stanford Bioengineering @bioe_stanford]

🎉 Congratulations to @MichaelCJewett for receiving the 2024 AIChE Food, Pharmaceutical, and Bioengineering Division Award at #AIChEAnnual @ChEnected! 🏆 This award honors outstanding contributions in chemical engineering within food, pharmaceuticals, and bioengineering.

[Ashty Karim @akarimlab]

@MarkBlenner @BlennerLab @UDChBE *whispers with excitement* she should apply to Northwestern!

[Ashty Karim @akarimlab]

Looking for talent to head the research arm of @NUSynBio ! If you are interested in shaping synthetic biology and you value creativity, impact, and great people, this is the opportunity for you. This is a fantastic job (I speak from experience!). Apply below!

[The Lucks Lab @LucksLab]

@NUSynBio is hiring a director of research! If you are interested in shaping a world class #synbio institution please apply!

https://t.co/07GMjeV2m1

[The Lucks Lab @LucksLab]

Preprint alert! Figuring out how to make 100s of cell-free biosensors on an @opentrons OT-2 robot. With @MichaelCJewett @akarimlab and a whole lot of other folks! On @biorxivpreprint now:

https://t.co/QwtMJK2dU4

[Ashty Karim @akarimlab]

Awesome day celebrating each other and our progress as a Center! @NUSynBio with a fantastic keynote from @delafuenteupenn on next-generation antimicrobials from ancient ancestral proteomes!

[Northwestern CSB @NUSynBio]

The 2024 CSB Annual Retreat is in full swing! How lucky are we to have such a talented, fun and collaborative community! #syntheticbiology

[Ashty Karim @akarimlab]

Developing high-throughput biology workflows can be plagued by variability. We identify some key variables and strategies to get the most from high-throughput cell-free experiments. Check it out!

[Michael C. Jewett @MichaelCJewett]

The "test" phase of #syntheticbiology research is slow. @holly_ekas @akarimlab @LucksLab @adsilverman627 Brenda Wang @NUSynBio speed this phase up by developing validation strategies for #cellfree workflows @ACSSynBio Editor's choice

https://t.co/804MvBVHyJ

[Javin Oza @ozalabCP]

DNA template is one of the most expensive and limiting components of #cellfree protein expression. @Jian_Li_SHT 's latest preprint helps address that problem.
https://t.co/TVBt5AjUlS

[Aristilde Lab @ Northwestern Engineering @AristildeLab]

Can wastewater bacteria provide solutions to the plastics problem? Just out today new @AristildeLab study unraveling how #wastewater Comamonas #bacteria break down PET #plastics into #nanoplastics and ultimately digestible #carbons. https://t.co/yJMnyQ5FR9

[Eshan | Better Bioeconomy ✉ @biotecheshan]

💨 @LanzaTech moves into the food arena with LanzaTech Nutritional Protein (LNP) set to reach commercial-scale production in 2028

'‘We ferment gases instead of sugars."

$LNZA

[Michael C. Jewett @MichaelCJewett]

Want to learn the newest innovations in #cellfree systems? Mark your calendar for the next Cell-Free Systems meeting to be held in Evanston @NorthwesternU next summer on August 20-22, 2025 with co-chairs @NehaPKamat @NUSynBio @MichaelKoepke80 @LanzaTech More info to come...

[Jessica Stark @JessicaCStark]

Join us @MITdeptofBE! We are searching for a tenure-track faculty colleague at the interface of #immunology and #biologicalengineering. Happy to answer questions about the BE department and junior faculty life at MIT (both great). Please share widely! https://t.co/xOFpH7bsKa

[Ashty Karim @akarimlab]

New work from the group applying cell-free protein engineering to develop metal binding sensors. We specifically modulate dynamic range and sensitivity of the PbrR transcription factor for lead detection at the legal limit. Check it out!

[Michael C. Jewett @MichaelCJewett]

Is your water safe to drink? Point-of-use diagnostics are needed to address the growing crisis of water security. With @holly_ekas Brenda Wang @akarimlab @LucksLab @NUSynBio we engineered a cell-free biosensor to detect lead at the legal limit @ACSSynBio
https://t.co/NfKtNtT5qX

[Ashty Karim @akarimlab]

@Jian_Li_SHT @MichaelCJewett Yes! Good times!

[Ashty Karim @akarimlab]

And the move into the new lab space is complete! Said goodbye to the Texas office (a decade of early scientist memories) 🥹…huge shoutout to @MichaelCJewett —advisor turned friend and colleague—(and his group) who was there to help me move in 🤩 now time to get to work📚🧫🥼

[Krishna Shrinivas @shrinivaslab]

Come be a fellow at @NITMB_Chicago if you are interested in math, theory, or bio (or any combination)!

Great opportunity for independent research + supportive community + mentorship + pot. collaborations with folks across @NorthwesternU @UChicago!

https://t.co/5YFlWvnyUO