Zeilstra-Ryalls This project focuses on a study of what factors regulate the intracellular levels of a key metabolite for essentially all living organisms, 5-aminolevulinic acid (ALA), using as a model system the photosynthetic bacterium Rhodobacter sphaeroides 2.4.1. ALA is the common precursor in the biosynthesis of such important biomolecules as heme, vitamin B12, and (bacterio)chlorophyll. R. sphaeroides 2.4.1 is a useful model because (a) unlike most prokaryotic organisms, it synthesizes ALA by the same condensation reaction, catalyzed by ALA synthase, between glycine and succinyl-CoA (Shemin pathway) used for ALA formation in fungal and animal cells, and it is the only prokaryote identified in which two genes (hemA and hemT) encoding ALA synthases are present, similar to the situation in higher organisms, including humans; (b) it synthesizes all of the ALA derivatives listed above; (c) its high metabolic versatility provides us with the ability to analyze how organisms sense and respond to their environment. The significance and importance of understanding the regulation of ALA synthesis is of unquestioned value because it is central to the formation of heme (present in cytrochromes and hemoglobin) required for aerobic and anaerobic respiration as well as oxygen transport, and chlorophyll required for photosynthesis. These studies will provide insights into the control of ALA synthesis in R. sphaeroides 2.4.1, and thus how this organism can sense its needs for tetrapyrroles and respond accordingly to changes in its growth conditions. A better understanding of tetrapyrrole biosynthesis in R. sphaeroides, will contribute to an understanding of tetrapyrrole synthesis in those organisms deploying the Shemin pathway.
