Antibiotics from Haloarchaea: What Can We Learn from Comparative Genomics?

The knowledge of antibiotics produced by Archaea (archaeocins) is still limited. So far, only two types of archaeocins are known: (i) sulfolobicins, produced by the extremely thermophilic Sulfolobus spp. and (ii) haloarcheocins, produced by halophilic archaea. Haloarcheocins were first discovered in the 1980s, but most of their characterisation was solely based on supernatant-based assays. Only a few were successfully purified and sequenced, and even fewer have a proposed biosynthetic model. Furthermore, their mode of action, ecological role and biotechnological potential are still to be explored. Haloarcheocin C8 (HalC8) is the best well-characterised haloarcheocin. We applied an approach of comparative genomics in order to go a step further in the knowledge of their biosynthetic clusters as well as the clusters encoding HalC8-like peptides. These peptides can be classified, at least, into 4 different clades, and there is low gene conservation between them. However, the putative function of some proteins is conserved. These include uncharacterized major facilitator superfamily proteins, transmembrane peptides, DNA-binding transcriptional regulators and proteins with extracellular domains. Our analysis reinforces the association of these proteins with HalC8/HalC8-like biosynthesis. Their functionality is unknown, and, in an era where it is known that haloarchaea are not confined to high salt habitats, the advance in the knowledge of their specialised metabolites will be imperative.