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Description
Overflow Metabolism is a seemingly wasteful metabolic strategy where fast-growing cells incompletely or inefficiently utilize their growth substrate through sub-optimal fermentative pathways and subsequently excrete metabolic intermediates as by-products. It is a ubiquitous phenotype that is conserved in all domains of life. Overflow Metabolism contradicts all contemporary concepts of metabolism, which often assume only the most efficient (respiratory) pathways promote optimal cell growth. The phenomenon suggests there are other, undetermined factors of cellular metabolism which are currently overlooked. Understanding the key principles which drive Overflow Metabolism is critical for fundamental concepts of metabolism which dictate cell growth and fitness, from cellular to organismal and ecosystem levels. Elucidating the interplay between fermentative and respiratory metabolic pathways can be used as leverage to guide further experiments. Methylotrophic prokaryotes are bacterial and archaeal species which utilize reduced single-carbon compounds such as methane, methanol, and methylamine as their sole carbon sources for biomass production. Their unique physiology, genetics, and metabolism allows them to be used as biocatalytic platforms with two main functions: industrial bioconversion and synthesizing compounds with high-added value. In this study, I focus on Methylotuvimicrobium alcaliphilum as a model to explore Overflow Metabolism in methanotrophic bacteria. Prior studies have demonstrated that M. alcaliphilum can transition to fermentative metabolism and excrete formate, despite having all the necessary resources for respiratory metabolism. Here, I employ M. alcaliphilum as a system to define and explore spatial cell properties in Overflow Metabolism via physiological (cell growth and organic acid secretion), microscopic (cell structure), and computational studies.
