Diversity of the heme-copper superfamily in archaea: insights from genomics and structural modeling

Recent advances in DNA sequencing technologies have provided unprecedented access into the diversity of the microbial world. Herein we use the comparative genomic analysis of microbial genomes and environmental metagenomes coupled with structural modelling to explore the diversity of aerobic respiration in Archaea. We focus on the heme-copper oxidoreductase superfamily which is responsible for catalyzing the terminal reaction in aerobic respiration-the reduction of molecular oxygen to water. Sequence analyses demonstrate that there are at least eight heme-copper oxygen reductase families: A-, B-, C-, D-, E-, F-, G-, and H-families. Interestingly, five of these oxygen reductase families (D-, E-, F-, G-, and H-families) are currently found exclusively in Archaea. We review the structural properties of all eight families focusing on the members found within Archaea. Structural modelling coupled with sequence analysis suggests that many of the oxygen reductases identified from thermophilic Archaea have modified proton channel properties compared to the currently studied mesophilic bacterial oxygen reductases. These structural differences may be due to adaptation to the specific environments in which these enzymes function. We conclude with a brief analysis of the phylogenetic distribution and evolution of Archaeal heme-copper oxygen reductases.