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Biosynthesis with heterologous production of mycosporine-like amino acid palythines

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eMediNexus    18 June 2021

A family of natural products known as mycosporine-like amino acids (MAAs) that are produced by a variation of organisms for protection from the damage of ultraviolet radiation. In this procedure, different bioinformatic approaches were combined to evaluate the distribution of the MAA biosynthesis and recognized a putative gene cluster from Nostoc linckia NIES-25 which encodes a short-chain dehydrogenase or reductase and a nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase (MysH) as probablethe new biosynthetic enzymes. 

Refactored gene clusters with heterologous expression in E. coli had produced two known biosynthetic intermediates, 4-deoxygadusol and mycosporine-glycine, along with three disubstituted MAA analogues, shinorine, porphyra-334, and mycosporine-glycine-alanine. The disubstituted MAAs were then converted into palythines by MysH. Also, biochemical characterization showed that the substrate preference of recombinant MysD, a d-Ala-d-Ala ligase-like enzyme is for the formation of disubstituted MAAs. This study will advance the biosynthetic understanding of a significant family of natural UV photo-protectants and also releases new opportunities to the development of next-generation sunscreens.

Source: Chen M, Rubin GM, Jiang G, Raad Z, Ding Y. Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines. J Org Chem. 2021 May 18. doi: 10.1021/acs.joc.1c00368. Epub ahead of print. PMID: 34006097. 

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