Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae

Kim, Sojeong; Park, Beom Gi; Jin, Hyunbin; Lee, Dongsoo; Teoh, Jie Ying; Kim, Yung Jae; Lee, S.Y.; Kim, Soo‐Jung; Moh, Sang Hyun; Yoo, Dongwon; Choi, Won Hoon; Hahn, Jinyong

doi:10.1016/j.ymben.2023.05.009

Cited by 10 publications

(9 citation statements)

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“…Various prokaryotes, including Escherichia coli , cyanobacteria, Corynebacterium glutamicum , and Streptomyces species, and the yeast S. cerevisiae , have been employed for MAAs production [ 10 – 13 , 15 ]. Notably, S. cerevisiae has shown promise as a host to produced MAAs compared to bacterial hosts [ 14 – 16 ]. In this study, we investigated the potential of Y. lipolytica as a chassis strain for MAAs production, leveraging its advantages such as a high pentose phosphate pathway flux and the ability to utilize a wide range of carbon sources.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the impact of xylose, we observed several distinctions in the production of MAAs between S. cerevisiae and Y. lipolytica . Firstly, despite we successfully expressed various MysD enzymes (D-Ala-D-Ala ligase homologues) in S. cerevisiae [ 14 – 16 ], we were unable to detect shinorine production upon the introduction of Av.mysE (NRPS-like enzyme) in S. cerevisiae (data not shown). Conversely, both Np.mysD and Av.mysE were functionally expressed in Y. lipolytica , indicating that Y. lipolytica is a more suitable chassis strain for expressing mysE .…”

Section: Discussionmentioning

confidence: 99%

“…While the level of MAAs produced in Y. lipolytica is currently lower than that attained in S. cerevisiae [ 14 ], there is a room for increased enhancement through additional metabolic engineering and optimization of fermentation conditions. Moreover, the distinctive cellular localization of MAAs and the utilization of a wide range of carbon sources could potentially offer advantages of using Y. lipolytica for the industrial-scale production of MAAs.…”

Section: Discussionmentioning

confidence: 99%

“…Although MAAs extracted from red algae are commercially available, the low yield and high cost of extraction make it impractical for large-scale production. Therefore, producing MAAs in heterologous microbial hosts are seen as a promising alternative [ 10 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we successfully engineered Saccharomyces cerevisiae to produce MAAs by introducing the MAA biosynthetic genes from cyanobacteria [ 14 – 16 ]. To enhance shinorine production, increasing the pool of S7P, the precursor for MAA biosynthesis, was critical.…”

Section: Introductionmentioning

confidence: 99%

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Efficient production of mycosporine-like amino acids, natural sunscreens, in Yarrowia lipolytica

Jin,

Kim,

Lee

et al. 2023

Biotechnol Biofuels

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Background Mycosporine-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. Results We 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. Conclusions Y. 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.

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