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Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale.
Fu, Jing; Zaghen, Simone; Lu, Hongzhong; Konzock, Oliver; Poorinmohammad, Naghmeh; Kornberg, Alexander; Ledesma-Amaro, Rodrigo; Koseto, Deni; Wentzel, Alexander; Di Bartolomeo, Francesca; Kerkhoven, Eduard J.
Afiliación
  • Fu J; Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
  • Zaghen S; Department of Bioengineering and Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
  • Lu H; Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
  • Konzock O; State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Poorinmohammad N; Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
  • Kornberg A; Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
  • Ledesma-Amaro R; Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
  • Koseto D; Department of Bioengineering and Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
  • Wentzel A; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim N-7465, Norway.
  • Di Bartolomeo F; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim N-7465, Norway.
  • Kerkhoven EJ; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim N-7465, Norway.
Sci Adv ; 10(32): eadn0414, 2024 Aug 09.
Article en En | MEDLINE | ID: mdl-39121230
ABSTRACT
Itaconic acid is an emerging platform chemical with extensive applications. Itaconic acid is currently produced by Aspergillus terreus through biological fermentation. However, A. terreus is a fungal pathogen that needs additional morphology controls, making itaconic acid production on industrial scale problematic. Here, we reprogrammed the Generally Recognized As Safe (GRAS) yeast Yarrowia lipolytica for competitive itaconic acid production. After preventing carbon sink into lipid accumulation, we evaluated itaconic acid production both inside and outside the mitochondria while fine-tuning its biosynthetic pathway. We then mimicked the regulation of nitrogen limitation in nitrogen-replete conditions by down-regulating NAD+-dependent isocitrate dehydrogenase through weak promoters, RNA interference, or CRISPR interference. Ultimately, we optimized fermentation parameters for fed-batch cultivations and produced itaconic acid titers of 130.1 grams per liter in 1-liter bioreactors and 94.8 grams per liter in a 50-liter bioreactor on semipilot scale. Our findings provide effective approaches to harness the GRAS microorganism Y. lipolytica for competitive industrial-scale production of itaconic acid.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinatos / Reactores Biológicos / Yarrowia / Fermentación Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinatos / Reactores Biológicos / Yarrowia / Fermentación Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos