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De Novo Synthesis of Resveratrol from Sucrose by Metabolically Engineered Yarrowia lipolytica.
Ibrahim, Gehad G; Perera, Madhavi; Abdulmalek, Saadiah A; Yan, Jinyong; Yan, Yunjun.
Afiliación
  • Ibrahim GG; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
  • Perera M; Department of Genetics, Faculty of Agriculture, Zagazig University, Zagazig 7120001, Egypt.
  • Abdulmalek SA; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
  • Yan J; Department of Electrical, Electronic and Telecommunication, Faculty of Engineering, General Sir John Kotelawala Defence University, Rathmalana 10390, Sri Lanka.
  • Yan Y; Department of Biology, Faculty of Science, Sana'a University, Sana'a 1247, Yemen.
Biomolecules ; 14(6)2024 Jun 16.
Article en En | MEDLINE | ID: mdl-38927115
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarosa / Yarrowia / Ingeniería Metabólica / Resveratrol Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarosa / Yarrowia / Ingeniería Metabólica / Resveratrol Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza