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Enzyme Rates in the Omics Era: From Global Characterization to a Pivotal Case Study
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Dissertation
Enzyme Rates in the Omics Era: From Global Characterization to a Pivotal Case Study
2019
Overview
Enzyme kinetics determine the rate of most biological processes. Decades of biochemistry have demonstrated how enzymes vary by orders of magnitude in their kinetic properties. Why are some enzymes faster than others and how are enzyme capacities related to cellular fitness? In my research I have focused on quantitative constraints on enzymes and metabolic networks. I have used Big Data in order to investigate the cellular cost of enzyme production, the efficiency of their utilization, and how design principles of metabolic networks shape enzyme kinetics and expression. I have been particularly interested in studying enzymatic catalysis directly inside cells, as opposed to classical biochemistry approaches, where enzymes are purified and evaluated outside of their cellular context. In the second part of my PhD I have looked into the interplay between the evolutionary drive to maximize enzyme efficiencies and the selection of other enzymatic traits such as substrate specificity - an interplay that results in often unexpected tradeoffs. These research directions have led me to begin to explore enzymatic tradeoffs in the most abundant, and some may say most-important, enzyme in the biosphere, Rubisco. In a large scale project, I am now working on exploring the kinetic space of Rubisco variants from nature - essentially looking for the best Rubisco in nature. Notably, at the end of this report there is a collection of “negative results”. Throughout the years, I have spend many hours on failed attempts. Here, I bring a collection of these attempts, computational or experimental with the hope that such a collection will encourage others to generate their own set of “negative results”. May this be a conceptual change which will accumulate to an invaluable resource for the scientific community
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798438788737
