Remodelling metabolism for high-level resveratrol production in Yarrowia lipolytica

Liu, Mengsu; Wang, Chao; Ren, Xuefeng; Gao, Song; Yu, Shiqin; Zhou, Jingwen

doi:10.1016/j.biortech.2022.128178

Cited by 30 publications

(35 citation statements)

References 45 publications

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“…As the proof, P. pastoris has been reformed to produce 1825 mg L −1 resveratrol and the engineering S. stipitis could produce resveratrol at a titer of 237.6 mg L −1 in glucose and 668.6 mg L −1 in sucrose (Kobayashi et al, 2021). In particular, the titer of resveratrol could attach 22.5 g L −1 in Y. lipolytica , which was the highest titer reported in yeast (M. Liu, Wang, et al, 2022). As to other stilbenes, resveratrol can be further methylated by resveratrol O ‐methyltransferase (ROMT) to generate pinostilbene and pterostilbene in S. cerevisiae (M. Li et al, 2016).…”

Section: P‐coumaric Acid Derivativesmentioning

confidence: 78%

“…Since the generation of resveratrol is directly influenced by the expression of 4CL and STS (Melkus et al, 2020), fusing 4CL and STS via an optimized flexible linker could eliminate the steric clash between 4CL and STS, thus resulting higher production of resveratrol (H. Guo et al, 2017; J. Li et al, 2016). For instance, the Zhou group fused 4CL and STS with a rigid linker (peptide sequence: EAAAK), and higher production of resveratrol was observed (M. Liu, Wang, et al, 2022). To improve the expression level of resveratrol biosynthesis genes, integration of multiple copies of key genes is useful.…”

Section: P‐coumaric Acid Derivativesmentioning

confidence: 99%

“…For example, an additional copy of TAL, 4CL and STS respectively increased the production of resveratrol over 1‐fold (Sáez‐Sáez et al, 2020). As for increasing the supply of malonyl‐CoA, the Zhou group knocked out diacylglycerol O‐acyltransferase 1 gene ( dga1 ) to avoid extra consume of malonyl‐CoA (M. Liu, Wang, et al, 2022).…”

Section: P‐coumaric Acid Derivativesmentioning

confidence: 99%

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Yeast: A platform for the production of _L‐tyrosine derivatives

Guo

et al. 2023

Yeast

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L -Tyrosine derivatives are widely applied in the pharmaceutical, food, and chemical industries. Their production is mainly confined to chemical synthesis and plant extract. Microorganisms, as cell factories, exhibit promising advantages for valuable chemical production to fulfill the increase in the demand of global markets. Yeast has been used to produce natural products owing to its robustness and genetic maneuverability. Focusing on the progress of yeast cell factories for the production of L -tyrosine derivatives, we summarized the emerging metabolic engineering approaches in building L -tyrosoineoverproducing yeast and constructing cell factories of three typical chemicals and their derivatives: tyrosol, p-coumaric acid, and L -DOPA. Finally, the challenges and opportunities of L -tyrosine derivatives production in yeast cell factories were also discussed.aromatic amino acids, cell factory, L -tyrosine derivatives, synthetic biology, yeastis an essential amino acid nutrient with diverse applications in food, medicine, and chemical industries. Its derivatives, including Hydroxytyrosol S. cerevisiae Glucose 5L fed-batch 6970 H. Liu, Wu, et al. (2022) Salidroside S. cerevisiae Glucose 5L fed-batch 26,550 H. Liu, Tian, et al. (2021) p-Coumaric acid derivatives p-coumaric acid S. cerevisiae Glucose 1L fed-batch 12,500 Q. Liu, Yu, et al. (2019) p-coumaric acid S. cerevisiae Xylose 1L fed-batch 242 Borja et al. (2019) Caffeic acid S. cerevisiae Carboxymethylcellulose Shake flask 16.91 M. Cai et al. (2022) Caffeic acid S. cerevisiae Glucose 1.2L fed-batch 5500 R. Chen et al. (2022) Caffeic acid Candida glycerinogenes Glucose and Xylose 5L fed-batch 431.45 X.-H. Wang et al. (2022) Rosmarinic acid S. cerevisiae Glucose Shake flask 208 P. Zhou et al. (2022) Ferulic Acid S. cerevisiae Glucose 1.2L fed-batch 3800 R. Chen et al. (2022) Resveratrol S. cerevisiae Glucose and Ethanol shake flask 187 Costa et al. (2021) Resveratrol S. cerevisiae Lactose Shake flask 210 Costa et al. (2022) Resveratrol Scheffersomyces stipitis Cellobiose Shake flask 529.8 Kobayashi et al. (2021) Resveratrol S. stipitis Sucrose Shake flask 668.6 Kobayashi et al. (2021) Resveratrol Pichia pastoris Glycerol 250 mL fed-batch 1825 Kumokita et al. (2022) Pterostilbene S. cerevisiae Glucose Shake flask 34.93 M. Li et al. (2016) Pinostilbene S. cerevisiae Glucose Shake flask 5.52 M. Li et al. (2016) Naringenin S. cerevisiae Glucose Shake flask 203.49 Tong et al. (2022) Naringenin S. cerevisiae Glucose 5L fed-batch 1184.1 H. Li et al. (2022) Naringenin Yarrowia lipolytica Glucose 3L fed-batch 898 Palmer et al. (2020) Naringenin P. pastoris Glycerol 250 mL fed-batch 1067 Kumokita et al. (2022) Naringenin Y. lipolytica Glucose Shake flask 252.4 Lv et al. (2019) Eriodictyol Y. lipolytica Glucose Shake flask 134.2 Lv et al. (2019) Phloretin S. cerevisiae Glucose 5L fed-batch 619.5 C. Jiang et al. (2020) Apigenin Y. lipolytica Glucose Shake flask 80.74 Vanegas et al. (2018) Luteolin Y. lipolytica Glucose Shake flask 47.9 Vanegas et al. (2018) Kaempferol S. ...

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Section: P‐coumaric Acid Derivativesmentioning

confidence: 78%

Section: P‐coumaric Acid Derivativesmentioning

confidence: 99%

Section: P‐coumaric Acid Derivativesmentioning

confidence: 99%

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Yeast: A platform for the production of _L‐tyrosine derivatives

Guo

et al. 2023

Yeast

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“…Through the integration of resveratrol intake and cardiorespiratory fitness increases strategies, cardiorespiratory fitness growth is promoted, and operations are gradually increased for humans [6]. Age-related cardiac disease is associated with numerous molecular and biochemical changes in the heart [7,8]. These changes affect cardiorespiratory fitness protein function increases and cardiac morphology resulting in alterations in cell signaling [9].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Supplements Reduce the Risk of Aging-Related Cardiac Disease after Cardiorespiratory Fitness

Wu¹,

Zhu²,

Li³

et al. 2023

Resveratrol - Recent Advances, Application, and Therapeutic Potential [Working Title]

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Aging changes in the very elderly cardiac disease are associated with physiological and pathological changes, however, all observed changes in aging are associated with a deterioration of cardiorespiratory fitness function. For example, hypertension and cardiorespiratory disease make difficult distinctions between normal aging changes and the effects of underlying resveratrol supplements processes. Cardiorespiratory fitness-independent changes in resveratrol intake are still unclear. This review aimed to discuss whether the aging-associated cardiorespiratory fitness changes in the heart can be reversed by resveratrol supplements, and the mechanisms of cardiorespiratory fitness. Aging led to apoptosis and fibrosis-related protein expression increased, however, cardiorespiratory fitness had revered more functions. Resveratrol supplements in combination with cardiorespiratory fitness had a good enhanced mitochondrial function in aging including IL-6, STAT3, MEK5, and MEK1/ERK1 increased. Resveratrol supplements also induced survival signals and downregulation of apoptosis signaling in aging. Therefore, we suggest resveratrol has enhanced cardiorespiratory fitness to combine their function in repressed aging.

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“…To date, microbes like Escherichia coli , Yarrowia lipolytica and Saccharomyces cerevisiae have been intensively explored for resveratrol production [ 5 ]. For ex novo production, the best recombinant E. coli produced 2.3 g/L resveratrol from p -coumaric acid [ 6 ] while for de novo biosynthesis, 0.8 g/L and 22.5 g/L resveratrol were obtained with S. cerevisiae and Y. lipolytica in bench-scale production, respectively [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Rhodotorula toruloides for resveratrol production

et al. 2022

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Background Resveratrol is a plant-derived phenylpropanoid with diverse biological activities and pharmacological applications. Plant-based extraction could not satisfy ever-increasing market demand, while chemical synthesis is impeded by the existence of toxic impurities. Microbial production of resveratrol offers a promising alternative to plant- and chemical-based processes. The non-conventional oleaginous yeast Rhodotorula toruloides is a potential workhorse for the production of resveratrol that endowed with an efficient and intrinsic bifunctional phenylalanine/tyrosine ammonia-lyase (RtPAL) and malonyl-CoA pool, which may facilitate the resveratrol synthesis when properly rewired. Results Resveratrol showed substantial stability and would not affect the R. toruloides growth during the yeast cultivation in flasks. The heterologus resveratrol biosynthesis pathway was established by introducing the 4-coumaroyl-CoA ligase (At4CL), and the stilbene synthase (VlSTS) from Arabidopsis thaliana and Vitis labrusca, respectively. Next, The resveratrol production was increased by 634% through employing the cinnamate-4-hydroxylase from A. thaliana (AtC4H), the fused protein At4CL::VlSTS, the cytochrome P450 reductase 2 from A. thaliana (AtATR2) and the endogenous cytochrome B5 of R. toruloides (RtCYB5). Then, the related endogenous pathways were optimized to affect a further 60% increase. Finally, the engineered strain produced a maximum titer of 125.2 mg/L resveratrol in YPD medium. Conclusion The non-conventional oleaginous yeast R. toruloides was engineered for the first time to produce resveratrol. Protein fusion, co-factor channeling, and ARO4 and ARO7 overexpression were efficient for improving resveratrol production. The results demonstrated the potential of R. toruloides for resveratrol and other phenylpropanoids production.

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Remodelling metabolism for high-level resveratrol production in Yarrowia lipolytica

Cited by 30 publications

References 45 publications

Yeast: A platform for the production of _L‐tyrosine derivatives

Yeast: A platform for the production of _L‐tyrosine derivatives

Resveratrol Supplements Reduce the Risk of Aging-Related Cardiac Disease after Cardiorespiratory Fitness

Metabolic engineering of Rhodotorula toruloides for resveratrol production

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Remodelling metabolism for high-level resveratrol production in Yarrowia lipolytica

Cited by 30 publications

References 45 publications

Yeast: A platform for the production of L‐tyrosine derivatives

Yeast: A platform for the production of L‐tyrosine derivatives

Resveratrol Supplements Reduce the Risk of Aging-Related Cardiac Disease after Cardiorespiratory Fitness

Metabolic engineering of Rhodotorula toruloides for resveratrol production

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Product

Resources

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Yeast: A platform for the production of _L‐tyrosine derivatives

Yeast: A platform for the production of _L‐tyrosine derivatives