Kinetics of Intracellular Protein Degradation in Bacteria

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Degradation of proteins within bacteria is an ongoing regulated process, which in concert with protein synthesis processes, determines the protein make-up of the cell and thus its transport and reaction properties. Under conditions of nutrient limitation, which are common to many bioprocesses or in genetically engineered cells, intracellular protein degradation rates are greatly accelerated. Intracellular protein breakdown contributes significantly to maintenance nutrient requirements in many bioprocess contexts and to loss of product yield in recombinant fermentations. This research will seek engineering kinetic descriptions of intracellular protein degradation, which can be used to guide organism and process design to maximize growth and product yields. In particular, this research will provide key data which are needed to improve kinetic models for bacterial growth and product synthesis under different growth conditions. This research addresses a central technical limitation in the manufacture of biochemicals, such as insulin and amino acids. After being synthesized within a genetically engineered cell, a protein product such as insulin is frequently attached and decomposed by digestive enzymes within that cell. Similarly, cells used to produce amino acids lose their capability to produce because critical proteins in those cells are inactivated by those cells' internal digestive enzymes. This research will study these degradative processes and how their rates might be reduced by careful choice of bioprocess operating conditions, such as temperature. Also, various genetic changes in the cell, which reduce its internal digestive activities, will be investigated to minimize productivity loses. The results of this research will be guidance of the genetic engineer and the biochemical engineer on ways to improve the useful production lifetime of the bioprocess. This lifetime is often a critical factor in successful process economic performance.