Heme biosynthesis and heme protein biogenesis
Nine different enzymes are required for heme B (protoheme IX) synthesis from glutamyl-tRNA in Bacillus subtilis. Current research is focused on the structure and mechanism of action of enzymes that transform heme B into heme A, heme C and heme D, respectively. Heme A is uniquely found in heme-copper respiratory terminal oxidases, i.e. in cytochromes of the a-type. Cytochromes of c–type contain covalently bound heme. Heme D is present in cytochrome bd respiratory terminal oxidases which only are found in bacteria. B. subtilis contains three terminal oxidases (2 cytochomes a and 1 cytochrome bd), four different cytochrome c. Enterococcus faecalis contain only one cytochrome (cytochrome bd) and assembly of this enzyme requires exogenously added heme.
After completion of heme B synthesis the heme is inserted into proteins or first enzymatically modified into another type of heme. Heme is not water soluble in the cell and is a toxic molecule especially in the reduced form and in the presence of dioxygen. It is not known how it is transported inside cells to its final destination. This transport is studied in Enterococcus faecalis which is an organism that does not depend on heme for growth but which can take up heme, and heme analogs, from the surroundings, transport it intracellularly, and incorporate it into protein to form different heme proteins. The current research focuses on understanding intracellular heme transport and assembly of heme proteins, includuing cytoplasmic catalase and membrane bound complex cytochromes.