Advances in the synthesis of three typical tetraterpenoids including β-carotene, lycopene and astaxanthin

Jing, Yiwen; Wang, Yanxia; Zhou, Dawei; Wang, Jingnan; Li, Jiawen; Sun, Jingxiang; Feng, Yifan; Xin, Fengxue; Zhang, Wenming

doi:10.1016/j.biotechadv.2022.108033

Cited by 33 publications

(24 citation statements)

References 131 publications

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“…During the construction of engineered strains, the integration of exogenous pathways can cause cytotoxicity, mainly due to substrate and cofactor competition and product toxicity . Carotenoids, such as β-carotene, lycopene, and astaxanthin, are hydrophobic compounds and primarily accumulate in the cell membrane and lipid bodies (Figure F) . The accumulation of carotenoids in cell membrane can disrupt the structure of the membrane, which could have a toxic effect on cells .…”

Section: Resultsmentioning

confidence: 99%

“…20 Carotenoids, such as β-carotene, lycopene, and astaxanthin, are hydrophobic compounds and primarily accumulate in the cell membrane and lipid bodies (Figure 4F). 10 The accumulation of carotenoids in cell membrane can disrupt the structure of the membrane, which could have a toxic effect on cells. 24 Additionally, excess β-carotene accumulation triggers yeast-tohypha transition, making it difficult to collect cells in Y. lipolytica.…”

Section: Extended Fermentation Time Was Restored Through Transporter ...mentioning

confidence: 99%

“…β-Carotene, with high added value, is usually obtained by chemical synthesis, plant extraction, and microbial fermentation . The β-carotene produced by microbial fermentation has a high biological activity and is not season restricted Y.…”

Section: Introductionmentioning

confidence: 99%

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Concomitant Production of Erythritol and β-Carotene by Engineered Yarrowia lipolytica

Zhang

et al. 2023

J. Agric. Food Chem.

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While the expansion of the erythritol production industry has resulted in unprecedented production of yeast cells, it also suffers from a lack of effective utilization. β-Carotene is a value-added compound that can be synthesized by engineered Yarrowia lipolytica. Here, we first evaluated the production performance of erythritol-producing yeast strains under two different morphologies and then successfully constructed a chassis with yeast-like morphology by deleting Mhy1 and Cla4 genes. Subsequently, β-carotene synthesis pathway genes, CarRA and CarB from Blakeslea trispora, were introduced to construct the βcarotene and erythritol coproducing Y. lipolytica strain ylmcc. The rate-limiting genes GGS1 and tHMG1 were overexpressed to increase the β-carotene yield by 45.32-fold compared with the strain ylmcc. However, increased β-carotene accumulation led to prolonged fermentation time; therefore, transporter engineering through overexpression of YTH1 and YTH3 genes was used to alleviate fermentation delays. Using batch fermentation in a 3 L bioreactor, this engineered Y. lipolytica strain produced erythritol with production, yield, and productivity values of 171 g/L, 0.56 g/g glucose, and 2.38 g/(L•h), respectively, with a concomitant βcarotene yield of 47.36 ± 0.06 mg/g DCW. The approach presented here improves the value of erythritol-producing cells and offers a low-cost technique to obtain hydrophobic terpenoids.

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Section: Resultsmentioning

confidence: 99%

Section: Extended Fermentation Time Was Restored Through Transporter ...mentioning

confidence: 99%

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Concomitant Production of Erythritol and β-Carotene by Engineered Yarrowia lipolytica

Zhang

et al. 2023

J. Agric. Food Chem.

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“…Generally, the lipid-soluble β-carotene is mainly stored in the cell membrane, which greatly reduces the flexibility of cell membranes, causing certain cytotoxicity to cells (Gao et al., 2017 ; Jing et al., 2022 ). The intracellular lipids of oleaginous yeasts can provide ideal intracellular storage space for β-carotene, which can effectively reduce the toxic effects of β-carotene on cells (Sun et al., 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Enhanced β-carotene production inYarrowia lipolyticathrough the metabolic and fermentation engineering

Jing

Wang

Gao

et al. 2023

Journal of Industrial Microbiology and Biotechnology

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β-Carotene is a kind of high-value tetraterpene compound, which shows various applications in medical, agricultural and industrial areas owing to its antioxidant, anti-tumor and anti-inflammatory activities. In this study, Yarrowia lipolytica was successfully metabolically modified through the construction and optimization of β-carotene biosynthetic pathway for β-carotene production. The β-carotene titer in the engineered strain Yli-C with the introduction of the carotenogenesis genes crtI crtE and crtYB can reach 34.5 mg/L. With the overexpression of key gene in MVA pathway and the enhanced expression of fatty acid synthesis pathway, the β-carotene titer of the engineered strain Yli-CAH reached 87 mg/L, which was 152% higher than that of the strain Yli-C. Through the further expression of the rate-limiting enzyme tHMGR and the copy number of β-carotene synthesis related genes, the β-carotene production of Yli-C2AH2 strain reached 117.5 mg/L. The final strain Yli-C2AH2 produced 2.7 g/L β-carotene titer by fed-batch fermentation in a 5.0 L fermenter. This research will greatly speed up the process of developing microbial cell factories for the commercial production of β-carotene.

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“…Generally, the lipid-soluble β-carotene is mainly stored in the cell membrane, which greatly reduces the exibility of cell membranes, causing certain cytotoxicity to cells 23,33 . The intracellular lipids of oleaginous yeasts can provide ideal intracellular storage space for β-carotene, which can effectively reduce the toxic effects of β-carotene on cells 34 .…”

Section: Enhancement Of Gene Expression Levels In Fatty Acid Synthesi...mentioning

confidence: 99%

Enhanced β-carotene production in Yarrowia lipolytica through the metabolic and fermentation engineering

Jing

Wang

Gao

et al. 2022

Preprint

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β-Carotene is a kind of high-value tetraterpene compound, which shows various applications in medical, agricultural and industrial areas owing to its antioxidant, anti-tumor and anti-inflammatory activities. In this study, Yarrowia lipolytica was successfully metabolically modified through the construction and optimization of β-carotene biosynthetic pathway for β-carotene production. The β-carotene titer in the engineered strain Yli-Cwith the introduction of the carotenogenesis genes crtI, crtEand crtYB can reach 34.5 mg/L. With the overexpression of key gene in MVA pathway and the enhanced expression of fatty acid synthesis pathway, the β-carotene titer of the engineered strain Yli-CAH reached 87 mg/L, which was 152% higher than that of the strain Yli-C. Through the further expression of the rate-limiting enzyme tHMGR and the copy number of β-carotene synthesis related genes, the β-carotene production of Yli-C2AH2 strain reached 117.5 mg/L. The final strain Yli-C2AH2 produced 2695.5 mg/L β-carotene titer by fed-batch fermentation in a 5.0 L fermenter. This research will greatly speed up the process of developing microbial cell factories for the commercial production of β-carotene.

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Advances in the synthesis of three typical tetraterpenoids including β-carotene, lycopene and astaxanthin

Cited by 33 publications

References 131 publications

Concomitant Production of Erythritol and β-Carotene by Engineered Yarrowia lipolytica

Concomitant Production of Erythritol and β-Carotene by Engineered Yarrowia lipolytica

Enhanced β-carotene production inYarrowia lipolyticathrough the metabolic and fermentation engineering

Enhanced β-carotene production in Yarrowia lipolytica through the metabolic and fermentation engineering

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