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Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale

Fu, Jing, 1985 (author)
Chalmers tekniska högskola,Chalmers University of Technology,Imperial College of Science, Technology and Medicine
Zaghen, Simone, 1996 (author)
Chalmers tekniska högskola,Chalmers University of Technology
Lu, Hongzhong, 1987 (author)
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Konzock, Oliver, 1991 (author)
Chalmers tekniska högskola,Chalmers University of Technology
Poorinmohammad, Naghmeh, 1989 (author)
Chalmers tekniska högskola,Chalmers University of Technology
Kornberg, Alexander (author)
Chalmers tekniska högskola,Chalmers University of Technology
Ledesma-Amaro, R. (author)
Imperial College of Science, Technology and Medicine
Koseto, Deni (author)
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Wentzel, Alexander (author)
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Di Bartolomeo, Francesca (author)
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Kerkhoven, Eduard, 1985 (author)
Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
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 (creator_code:org_t)
2024
2024
English.
In: Science advances. - 2375-2548. ; 10:32, s. eadn0414-
Related links:
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

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