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De Novo Synthesis of Resveratrol from Sucrose by Metabolically Engineered Yarrowia lipolytica
Faculty
Agriculture
Year:
2024
Type of Publication:
ZU Hosted
Pages:
Authors:
Gihad Gomaa Attia Ibrahim
Staff Zu Site
Abstract In Staff Site
Journal:
Biomolecules MDPI
Volume:
Keywords :
, Novo Synthesis , Resveratrol from Sucrose , Metabolically
Abstract:
Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. Yarrowia lipolytica stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer Y. lipolytica for resveratrol production. The resveratrol biosynthetic pathway was integrated into Y. lipolytica by adding genes encoding tyrosine ammonia lyase from Rhodotorula glutinis, 4-coumarate CoA ligase from Nicotiana tabacum, and stilbene synthase from Vitis vinifera. This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from Arabidopsis thaliana, malonyl-CoA synthase, and a malonate transporter protein from Bradyrhizobium diazoefficiens. These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of Y. lipolytica as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production.
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Gihad Gomaa Attia Ibrahim, "Microbial Production of Resveratrol", Springer, Cham, 2022
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Gihad Gomaa Attia Ibrahim, "Resveratrol production in yeast hosts: current status and perspectives", MDPI, 2021
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Department Related Publications
Ahmed Salaheldeen Mohamed Abdelrahman Eldomyaty, "IDENTIFICATION OF MOLECULAR MARKERS FOR SALT AND DROUGHT TOLERANCE USING BULKED SEGREGANT ANALYSIS (BSA) IN BREAD WHEAT (Triticum aestivum L.)", Zagazig Journal of Agricultural Research, 2014
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Abdallah Abdelaziem Hassanin Safan, "Purification and Modes of Antifungal Actionby Vicia faba cv. Egypt Trypsin Inhibitor", School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China., 2010
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Abdallah Abdelaziem Hassanin Safan, "Isolation of a New Trypsin Inhibitor from the Faba Bean (Vicia faba cv.Giza 843) with Potential Medicinal Applications", School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China., 2011
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