Dataset Information

Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

ABSTRACT: 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.

SUBMITTER: Chen M

PROVIDER: S-EPMC8905528 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

Chen Manyun M Rubin Garret M GM Jiang Guangde G Raad Zachary Z Ding Yousong Y

The Journal of organic chemistry 20210518 16

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 <i>Nostoc linckia</i> 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. H ...[more]

PMID: 34006097

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Project description:BackgroundMycosporine-like amino acids (MAAs), including shinorine and porphyra-334, are gaining attention as safe natural sunscreens. The production of MAAs has been achieved in diverse microbial hosts, including Saccharomyces cerevisiae. While S. cerevisiae is the most extensively studied model yeast, the oleaginous yeast Yarrowia lipolytica has emerged as a promising candidate for the synthesis of valuable products. In this study, we explored the potential of Y. lipolytica as a host for producing MAAs, utilizing its advantages such as a robust pentose phosphate pathway flux and versatile carbon source utilization.ResultsWe produced MAAs in Y. lipolytica by introducing the MAA biosynthetic genes from cyanobacteria Nostoc punctiforme and Anabaena variabilis. These genes include mysA, mysB, and mysC responsible for producing mycosporine-glycine (MG) from sedoheptulose 7-phosphate (S7P). The two strains utilize different enzymes, D-Ala-D-Ala ligase homologue (MysD) in N. punctiforme and NRPS-like enzyme (MysE) in A. variabilis, for amino acid conjugation to MG. MysE specifically generated shinorine, a serine conjugate of MG, while MysD exhibited substrate promiscuity, yielding both shinorine and a small amount of porphyra-334, a threonine conjugate of MG. We enhanced MAAs production by selecting mysA, mysB, and mysC from A. variabilis and mysD from N. punctiforme based on their activities. We further improved production by strengthening promoters, increasing gene copies, and introducing the xylose utilization pathway. Co-utilization of xylose with glucose or glycerol increased MAAs production by boosting the S7P pool through the pentose phosphate pathway. Overexpressing GND1 and ZWF1, key genes in the pentose phosphate pathway, further enhanced MAAs production. The highest achieved MAAs level was 249.0 mg/L (207.4 mg/L shinorine and 41.6 mg/L of porphyra-334) in YP medium containing 10 g/L glucose and 10 g/L xylose.ConclusionsY. lipolytica was successfully engineered to produce MAAs, primarily shinorine. This achievement involved the introduction of MAA biosynthetic genes from cyanobacteria, establishing xylose utilizing pathway, and overexpressing the pentose phosphate pathway genes. These results highlight the potential of Y. lipolytica as a promising yeast chassis strain for MAAs production, notably attributed to its proficient expression of MysE enzyme, which remains non-functional in S. cerevisiae, and versatile utilization of carbon sources like glycerol.

Dataset Information

Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

Publications

Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

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