Archaeal heme a synthase: evolutionary trajectory distinct from bacterial homologs

Hemes are iron-containing porphyrin compounds that play a crucial role in a wide array of biological processes. Heme <i>a</i> synthase (HAS) is a crucial enzyme that facilitates the biosynthesis of heme <i>a</i>, an essential heme variant that serves as a cofactor in heme-copper terminal oxidases and in some acidophilic archaea's quinol reductases, such as the <i>ba</i> complex. Depending on the length and presence or absence of cysteine residues in the periplasmic loop(s), HAS has been classified into different types. Our manuscript presents a large-scale analysis of the distribution and evolution of HAS in Archaea in comparison to Bacteria, revealing evolutionary patterns among the proposed subtypes, with types 1 and 2 diverging early. This study also underscores the complexity of HAS enzyme evolution, which reflects deep ancestral innovations as well as recent ecological pressures.