Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines

Mycosporine-like amino acids (MAAs) are a family of natural products that are produced by a variety of organisms for protection from ultraviolet damage. In this work, we combined different bioinformatic approaches to assess the distribution of the MAA biosynthesis and identified a putative gene cluster from Nostoc linckia NIES-25 that encodes a short-chain dehydrogenase/reductase and a nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase (MysH) as potential new biosynthetic enzymes. Heterologous expression of refactored gene clusters in E. coli produced two known biosynthetic intermediates, 4-deoxygadusol and mycosporine-glycine, and three disubstituted MAA analogues, porphyra-334, shinorine, and mycosporine-glycine-alanine. Importantly, the disubstituted MAAs were converted into palythines by MysH. Furthermore, biochemical characterization revealed the substrate preference of recombinant MysD, a D-Ala-D-Ala ligase-like enzyme for the formation of disubstituted MAAs. Our study advances the biosynthetic understanding of an important family of natural UV photoprotectants and opens new opportunities to the development of next-generation sunscreens.

Automated summary

The study utilized various bioinformatic approaches to evaluate the distribution of MAA biosynthesis, identified a new gene cluster encoding potential biosynthetic enzymes from Nostoc linckia NIES-25, and successfully expressed them heterologously in E. coli. This research advances the understanding of the biosynthetic mechanisms of this important family of natural UV photoprotectants.