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Talk by Assoc. Prof. Dr. Ahmed H. Badran: Exploring RuBisCO Function Using Synthetic Biology

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Strategies to study or improve the biochemical properties of the ubiquitous photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) often link CO2 fixation to bacterial growth. However, such viability-driven phenotypes may not directly reflect RuBisCO carboxylation kinetics and can be confounded by toxicity of the RuBisCO substrate RuBP as well as differences in expression between RuBisCO homologs. In this presentation, Assoc. Prof. Dr. Ahmed H. Badran will discuss his teams efforts to develop a genetically encoded system to accurately and rapidly assess RuBisCO-dependent CO2 fixation kinetics in cells in a viability-independent manner. This approach combines organisms that insulate RuBisCO-derived products from host metabolism, engineered enzymes that improve gene circuit tolerance, and biosensors to monitor intracellular RuBisCO abundance and catalysis. This strategy is compatible with RuBisCOs from all clades, and can be readily used to improve the carboxylation kinetics of RuBisCO. This study highlights the combined power of metabolic engineering and retro-biosynthesis, and provides a novel resource for the discovery of RuBisCOs with improved CO2 fixation capabilities alongside traditional viability-driven selections.

Ahmed H. Badran is an Associate Professor in the Departments of Chemistry and of Integrative Structural and Computational Biology at the Scripps Research Institute. Badran earned his B.Sc. in Biochemistry & Molecular Biophysics from the University of Arizona. As an NSF Graduate Research Fellow at Harvard University, Badran developed high-throughput strategies to evolve proteins with improved or altered activities. After receiving his Ph.D. in 2016, he was selected as part of the first class of Fellows of the Broad Institute of Harvard and MIT, where his group developed technologies to alter protein translation and expand the genetic code of cells. He moved to the Scripps Research Institute in 2021, where his on-going research leverages the programmability of biological systems to develop next-generation strategies for addressing global problems in biotechnology, medicine, and sustainability. Badran’s current research interests include engineering of carbon-sequestering enzymes; development of pathogen-specific antimicrobials to curb widespread resistance; creating new-to-nature catalysts that bridge synthetic chemistry and molecular biology; and pioneering novel bioactive modalities to therapeutically intervene in diverse disease states.