Nine different enzymes are required for heme B (protoheme IX) synthesis from glutamyl-tRNA in Bacillus subtilis. We have previously cloned genes for these enzymes. Current work is focused on the structure and mechanism of action of enzymes that transform heme B into heme A and heme C. Heme A is uniquely found in respiratory terminal oxidases, i.e. in cytochromes of the a-type. In B. subtilis we have identified two gene products required for heme A synthesis from heme B, CtaA and CtaB which both are integral membrane proteins. The evolution, structure and mechanism of function of CtaA proteins from B. subtilis and the hyperthermophile Aeropyrum pernix are now studied in detail.
Cytochromes of c-type differ from other cytochromes in that the heme is covalently bound and that in bacteria the heme-containing domain always is located on the outer side of the cytoplasmic membrane. In a genetic approach we search in B. subtilis for components (heme transporter, disulfide isomerases, heme lyase etc) required for cytochrome c synthesis. So far we have identified four proteins that function in cytochrome c synthesis in B. subtilis: the CcdA ResA, ResB and ResC proteins.