Defining the Biological Importance and Conservation of Heme Degrading Enzymes

Abstract

The goal of this thesis was to investigate the role of the IsdG family of heme oxygenases within microbial cells. In Chapter II, I identified the first IsdG family member in a eukaryotic organism and expanded the IsdG family from 22 protein members to 866. C. reinhardtii is the first organism which contains both HO-1 and IsdG family heme oxygenases. Intriguingly, LFO1 is the only heme oxygenase whose transcription is upregulated under low iron conditions, a condition where the cytochrome associated with the photosynthetic complexes in the chloroplast are degraded and heme is released into the chloroplast cytoplasm. I have hypothesized that LFO1 is important for degradation of this heme and in iron recycling under these iron limited conditions. Additionally, during the process of trying to determine the role of the IsdG family heme catabolites within S. aureus, in Chapter III I elucidated the importance of Fur regulation of the heme oxygenases. Removing the inhibition of transcription by Fur under iron replete conditions, the heme oxygenases led to degradation of endogenously biosynthesized heme and an increased reliance on fermentation for energy production. In total, these studies have displayed the importance of the IsdG family of heme oxygenases for iron recycling and heme homeostasis within organisms from different domains of life.