Ljubisa Miskovic

Abstract Dynamic (kinetic) models track time-varying metabolite concentrations, fluxes, and enzyme levels, quantifying responses to genetic and environmental perturbations. Yet building these models at scale is hindered by scarce enzyme kinetic parameters. Generative neural networks can rapidly parameterize near-genome-scale kinetic models, but their representations are hard to interpret and often require new training to move across species or physiological states.

Abstract Devising genetic interventions for desired cellular phenotypes remains challenging regarding time and resources. Kinetic models can accelerate this task by simulating metabolic responses to genetic perturbations. However, exhaustive design evaluations with kinetic models are computationally impractical, especially when targeting multiple enzymes. Here, we introduce a framework for efficiently scouting the design space while respecting cellular physiological requirements.

Abstract Novel sequencing techniques and biochemical pathway prediction resources provide a wealth of data on novel proteins and computationally predicted enzymatic reactions. Accurate matching of protein sequences to enzymatic activities is crucial for advancing synthetic biology and metabolic engineering efforts. Here we present BridgIT+, a computational workflow that accounts for enzyme promiscuity and accurately predicts protein-reaction and reaction-protein associations.