Abstract:Hydroxytyrosol (HT) is a valuable aromatic compound with numerous applications. Herein, we enabled the efficient and scalable de novo HT production in engineered Saccharomyces cerevisiae (S. cerevisiae) from glucose. Starting from a tyrosol-overproducing strain, six HpaB/HpaC combinations were investigated, and the best catalytic performance was acquired with HpaB from Pseudomonas aeruginosa (PaHpaB) and HpaC from Escherichia coli (EcHpaC), resulting in 425.7 mg/L HT in shake flasks. Next, weakening the trypto… Show more
“…The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022). On the other hand, enriching the tyrosol's supply represents an efficient method for producing hydroxytyrosol (Bisquert et al, 2022; Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The Lyu group compared different sugars in the production of hydroxytyrosol, and the production of hydroxytyrosol was improved by three‐fold with the usage of sucrose and glycerol as carbon source than that of glucose (Y. Liu, Liu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 92%
“…However, the HpaBC‐based reaction has a low yield of hydroxytyrosol in yeast (Y. Liu, Song, et al, 2022). To improve the conversion rate, researchers tested the effects of different combination of HpaB and HpaC (Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 99%
“…To improve the conversion rate, researchers tested the effects of different combination of HpaB and HpaC (Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022). On the other hand, enriching the tyrosol's supply represents an efficient method for producing hydroxytyrosol (Bisquert et al, 2022; Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 99%
“…The Lyu group compared different sugars in the production of hydroxytyrosol, and the production of hydroxytyrosol was improved by three‐fold with the usage of sucrose and glycerol as carbon source than that of glucose (Y. Liu, Liu, et al, 2022). Our group improved the cofactor supply by introducing the mutant of TyrA M53I A354V , and 6.97 g L −1 production of hydroxytyrosol in fed‐batch was achieved (H. Liu, Wu, et al, 2022). Taking that Escherichia coli may be a better platform to hydroxylate tyrosol, the Lyu group adopted a S. cerevisiae ‐ E. coli coculture strategy and placed the hydroxylation of tyrosol in E. coli with 435 mg L −1 hydroxytyrosol produced in fermentation (Y. Liu, Gue, et al, 2022).…”
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. ...
“…The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022). On the other hand, enriching the tyrosol's supply represents an efficient method for producing hydroxytyrosol (Bisquert et al, 2022; Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The Lyu group compared different sugars in the production of hydroxytyrosol, and the production of hydroxytyrosol was improved by three‐fold with the usage of sucrose and glycerol as carbon source than that of glucose (Y. Liu, Liu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 92%
“…However, the HpaBC‐based reaction has a low yield of hydroxytyrosol in yeast (Y. Liu, Song, et al, 2022). To improve the conversion rate, researchers tested the effects of different combination of HpaB and HpaC (Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 99%
“…To improve the conversion rate, researchers tested the effects of different combination of HpaB and HpaC (Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022). The best combination Pa HpaB‐ Ec HpaC results more than 2‐fold production of hydroxytyrosol than others (H. Liu, Wu, et al, 2022). On the other hand, enriching the tyrosol's supply represents an efficient method for producing hydroxytyrosol (Bisquert et al, 2022; Y. Liu, Liu, et al, 2022; H. Liu, Wu, et al, 2022).…”
Section: Tyrosol Derivativesmentioning
confidence: 99%
“…The Lyu group compared different sugars in the production of hydroxytyrosol, and the production of hydroxytyrosol was improved by three‐fold with the usage of sucrose and glycerol as carbon source than that of glucose (Y. Liu, Liu, et al, 2022). Our group improved the cofactor supply by introducing the mutant of TyrA M53I A354V , and 6.97 g L −1 production of hydroxytyrosol in fed‐batch was achieved (H. Liu, Wu, et al, 2022). Taking that Escherichia coli may be a better platform to hydroxylate tyrosol, the Lyu group adopted a S. cerevisiae ‐ E. coli coculture strategy and placed the hydroxylation of tyrosol in E. coli with 435 mg L −1 hydroxytyrosol produced in fermentation (Y. Liu, Gue, et al, 2022).…”
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. ...
“…A recent study using chromosomally engineered S. cerevisiae and glucose produced HT with a titer of 6.97 g/L in fed-batch cultivation, which is extremely high . However, the net titer of HT from glucose was unclear because a small amount of Tyr, which is a source of HT via the Ehrlich pathway, was supplied to the culture with the peptone and yeast extract.…”
3-Hydroxytyrosol (HT) is a super antioxidant possessing
many physiological
advantages for human health. However, the extraction of natural HT
from olive (Olea europaea) is expensive,
and its chemical synthesis presents an environmental burden. Therefore,
microbial production of HT from renewable sources has been investigated
over the past decade. In the present study, we modified the chromosome
of a phenylalanine-producing strain of Escherichia
coli to generate an HT-producing strain. The initial
strain showed good HT production in tests performed by test tube cultivation,
but this performance did not transfer to jar-fermenter cultivation.
To grow well and achieve higher titers, the chromosome was further
engineered and the cultivation conditions were further modified. The
final strain achieved a higher HT titer (8.8 g/L) and yield (8.7%)
from glucose in the defined synthetic medium. These yields are the
best reported to date for the biosynthesis of HT from glucose.
Abstract4‐Hydroxy‐2,5‐dimethyl‐3(2H)‐furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor‐enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii, and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR. The HDMF production of the ZrQOR strain was significantly higher than that of wild‐type Z. rouxii at 3 and 5 days of culture, with 1.41‐fold and 1.08‐fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii. At 3, 5, and 7 days, QOR gene expression was 4.8‐fold, 3.3‐fold, and 5.6‐fold higher in the ZrQOR strain than in the wild‐type Z. rouxii, respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0–20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis.
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