Resolving Confusion Surroundingd‐Ala‐d‐Ala Ligase Catalysis in Cyanobacterial Mycosporine‐Like Amino Acid (MAA) Biosynthesis

Abstract

Mycosporine-like amino acids (MAAs) are natural UV-absorbing sunscreens that evolved in cyanobacteria and algae to palliate harmful effects from obligatory exposure to solar radiation. Multiple lines of evidence prove that in cyanobacteria all MAAs are derived from mycosporine-glycine, which is typically modified by an ATP-dependent ligase encoded by the gene mysD. The function of the mysD ligase has been experimentally described but haphazardly named based solely upon sequence similarity to the d-alanine-d-alanine ligase of bacterial peptidoglycan biosynthesis. Combining phylogeny and alpha-fold tertiary protein structure prediction unambiguously distinguished mysD from d-alanine-d-alanine ligase. The renaming of mysD to mycosporine-glycine-amine ligase (MG-amine ligase) using recognised enzymology rules of nomenclature is, therefore, proposed, and considers relaxed specificity for several different amino acid substrates. The evolutionary and ecological context of MG-amine ligase catalysis merits wider appreciation especially when considering exploiting cyanobacteria for biotechnology, for example, producing mixtures of MAAs with enhanced optical or antioxidant properties.

Environmental adaptations by the intertidal Antarctic cyanobacterium Halotia branconiiCENA392 as revealed using long‐read genome sequencing

“…This cluster was also automatically located with the antiSMASH analysis, showing considerable sequence similarity (> 75%) to other Nostocales strains. The mysD gene (encoding for the recently renamed mycosporine-glycine-amine ligase, Dextro et al 2023b) was located over 1,500,000 bp downstream from the cluster. This suggested that this gene homolog was probably unrelated to MAA biosynthesis, and more likely associated with other biochemical pathways such as peptidoglycan biosynthesis (Walsh 1989).…”