Accelerated Enzyme Engineering With Transcription Factors

Event details
Date | 23.06.2025 |
Hour | 12:00 › 13:00 |
Speaker | Simon d'Oelsnitz, Ph.D., Synthetic Biology HIVE and Wyss Institute, Harvard Medical School, Cambridge/Boston, MA (USA) |
Location | Online |
Category | Conferences - Seminars |
Event Language | English |
BIOENGINEERING SEMINAR
Abstract:
Enzymes are becoming indispensable catalysts for pharmaceutical manufacturing, but often must be engineered in a process bottlenecked by low-throughput chromatographic screens. Prokaryotic transcription factors (TFs) can overcome this limitation by converting enzyme reaction products into programmable genetic outputs. In this seminar, I will discuss methods for engineering and applying TF biosensors to rapidly improve industrially relevant enzymes. Growth and fluorescence-coupled screens are used to rapidly generate highly specific alkaloid biosensors, which enable the directed evolution of regioselective plant methyltransferases. A massively parallel reporter assay is then used to quantitatively measure the specificity of >300,000 biosensor variants for pharmaceutical intermediates. Finally, biosensor-coupled fluorescence activated cell sorting is used to profile the enantioselectivity of a large imine reductase library. By linking molecular chemistry to programmable genetics, TF biosensors promise to accelerate the development of enzymes for pharmaceutical manufacturing and beyond.
Bio:
Simon is a Synthetic Biology Fellow at Harvard Medical School working at the Synthetic Biology HIVE and the Wyss Institute. He has an undergraduate degree in Pharmacology from Stony Brook University. From 2016 to 2021, he completed his PhD at The University of Texas at Austin with Andy Ellington and Hal Alper where he used directed evolution to engineer proteins that interact with small molecules, including biosensors, enzymes, aminoacyl-tRNA synthetases, and transporters. From 2021 to 2023, he developed new measurement techniques to profile large biosensor libraries with the Cellular Engineering Group at the National Institute of Standards and Technology (NIST). Since 2023, Simon has led a subgroup at Harvard Medical School focused on developing and applying chemical-responsive biosensors.
Zoom link for attending remotely: https://https://epfl.zoom.us/j/68799552819
Instructions for 1st-year Ph.D. students planning to attend this talk, who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
Abstract:
Enzymes are becoming indispensable catalysts for pharmaceutical manufacturing, but often must be engineered in a process bottlenecked by low-throughput chromatographic screens. Prokaryotic transcription factors (TFs) can overcome this limitation by converting enzyme reaction products into programmable genetic outputs. In this seminar, I will discuss methods for engineering and applying TF biosensors to rapidly improve industrially relevant enzymes. Growth and fluorescence-coupled screens are used to rapidly generate highly specific alkaloid biosensors, which enable the directed evolution of regioselective plant methyltransferases. A massively parallel reporter assay is then used to quantitatively measure the specificity of >300,000 biosensor variants for pharmaceutical intermediates. Finally, biosensor-coupled fluorescence activated cell sorting is used to profile the enantioselectivity of a large imine reductase library. By linking molecular chemistry to programmable genetics, TF biosensors promise to accelerate the development of enzymes for pharmaceutical manufacturing and beyond.
Bio:
Simon is a Synthetic Biology Fellow at Harvard Medical School working at the Synthetic Biology HIVE and the Wyss Institute. He has an undergraduate degree in Pharmacology from Stony Brook University. From 2016 to 2021, he completed his PhD at The University of Texas at Austin with Andy Ellington and Hal Alper where he used directed evolution to engineer proteins that interact with small molecules, including biosensors, enzymes, aminoacyl-tRNA synthetases, and transporters. From 2021 to 2023, he developed new measurement techniques to profile large biosensor libraries with the Cellular Engineering Group at the National Institute of Standards and Technology (NIST). Since 2023, Simon has led a subgroup at Harvard Medical School focused on developing and applying chemical-responsive biosensors.
Zoom link for attending remotely: https://https://epfl.zoom.us/j/68799552819
Instructions for 1st-year Ph.D. students planning to attend this talk, who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
- send D. Reinhard a note well ahead of time (ideally before seminar day), informing that you plan to attend the talk online, and, during seminar:
- be signed in on Zoom with a recognizable user name (not any alias making it difficult or impossible to identify you).
Practical information
- Informed public
- Free
Organizer
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD