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 a synthase (HAS) is a crucial enzyme that facilitates the biosynthesis of heme a, 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 ba 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.