Metabolic engineering of Yarrowia lipolytica for liquiritigenin production

Akram, Muhammad; Rasool, Aamir; An, Ting; Feng, Xudong; Li, Chun

doi:10.1016/j.ces.2020.116177

Cited by 23 publications

(25 citation statements)

References 67 publications

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“…The synthesis of liquiritigenin de novo in yeast has been realized in S. cerevisiae and Yarrowia lipolytica [42,43]. The nal liquiritigenin titer of one Y. lipolytica strain was 62.4 mg/L [42].…”

Section: Metabolite Accumulation In the Fermenter Varies With The Amo...mentioning

confidence: 99%

Heterogenous biosynthesis of medicarpin using engineered Saccharomyces cerevisiae

Lu¹,

et al. 2023

Preprint

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Background Medicarpin is one important bioactive compound with multiple medicinal activities, including anti-tumor, anti-osteoporosis, anti-bacterial effects. Medicarpin is assigned to pterocarpans derived from medicinal plants, such as Sophora japonica, Glycyrrhiza uralensisFisch. and Glycyrrhiza glabra L.However, these medicinal plants only contain low amounts of medicarpin. Moreover, the planting area for medicarpin-producing plants is limited, thus, current medicarpin supply cannot satisfy the great demands of medicinal markets. Results In this study, eight key genes involved in medicarpin biosynthesis were identified by comparative transcriptome analysis and bioinformatic analyses. In vitro and in vivoenzymatic activities assays confirmed the catalytic functions of candidate enzymes were responsible for the biosynthesis of medicarpin and medicarpin intermediates. Further engineering of these genes in Saccharomyces cerevisiae achieved the heterogenous biosynthesis of medicarpin using liquiritigenin as the substrate, and the final medicarpin titer was 0.82 ± 0.18 mg/L. By increasing the gene copy number of VRand PTS, the final titer of the medicarpin increased to 2.05 ± 0.72 mg/L. Conclusion This study provides a solid foundation for the economical and sustainable production of medicarpin by synthetic biology strategy.

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Section: Metabolite Accumulation In the Fermenter Varies With The Amo...mentioning

confidence: 99%

Heterogenous biosynthesis of medicarpin using engineered Saccharomyces cerevisiae

Lu¹,

et al. 2023

Preprint

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“…Aglycone is the nonglycoside part condensed with glycoside. The heterologous synthesis of some flavonoid aglycones has been engineered in cells and includes (2 S )-naringenin, quercetin, and liquiritigenin . Gao et al used Saccharomyces cerevisiae as a host to efficiently convert p -coumaric acid to (2 S )-naringenin and optimized the process by fed-batch fermentation to generate 648.63 mg/L .…”

Section: Introductionmentioning

confidence: 99%

“…The heterologous synthesis of some flavonoid aglycones has been engineered in cells and includes (2S)-naringenin, quercetin, and liquiritigenin. 3 Gao et al used Saccharomyces cerevisiae as a host to efficiently convert pcoumaric acid to (2S)-naringenin and optimized the process by fed-batch fermentation to generate 648.63 mg/L. 4 A fatty acid catabolism strategy was also used to produce (2S)-naringenin and improve titer levels to 1129.44 mg/L.…”

Section: Introductionmentioning

confidence: 99%

Glycosylation Modification Enhances (2S)-Naringenin Production in Saccharomyces cerevisiae

Lyv

et al. 2022

ACS Synth. Biol.

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(2S)-Naringenin is an important flavonoid precursor, with multiple nutritional and pharmacological activities. Both (2S)-naringenin and other flavonoid production are hindered by poor water solubility and inhibited cell growth. To address this, we increased solubility and improved cell growth by partially glycosylating (2S)-naringenin to naringenin-7-O-glucoside, which facilitated increased extracellular secretion, by knocking out endogenous glycosyl hydrolase genes, EXG1 and SPR1, and expressing the glycosyltransferase gene (UGT733C6). Naringenin-7-O-glucoside synthesis was further improved by optimizing UDP-glucose and shikimate pathways. Then, hydrochloric acid was used to hydrolyze naringenin-7-O-glucoside to (2S)-naringenin outside the cell. Thus, our optimized Saccharomyces cerevisiae strain E32T19 produced 1184.1 mg/L (2S)-naringenin, a 7.9-fold increase on the starting strain. Therefore. we propose that glycosylation modification is a useful strategy for the efficient heterologous biosynthesis of (2S)-naringenin in S. cerevisiae.

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“…Furthermore, genetic manipulation tools have been developed in Y. lipolytica through engineering DNA double-strand break (DSB) repair protein complex Ku70/Ku80 [ 27 , 28 ]. So far, several efforts have been made to utilize Y. lipolytica as platform to produce natural products ( Supplementary Table S1 ) and the highest yield of resveratrol has reached to 12 g/L [ [29] , [30] , [31] , [32] , [33] , [34] , [35] ]. More importantly, naringenin and arbutin have been successfully produced, indicating sufficient precursor and abundant glycosylated donor of scutellarin in Y. lipolytica [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%