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Fine-tuning of p-co...
Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast
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- Mao, Jiwei, 1990 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Tous Mohedano, Marta, 1995 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Fu, Jing, 1985 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Li, Xiaowei, 1986 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Liu, Quanli, 1988 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Nielsen, Jens B, 1962 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology,BioInnovation Institute (BII)
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- Siewers, Verena, 1976 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Chen, Yun, 1978 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Metabolic Engineering. - 1096-7176 .- 1096-7184. ; 79, s. 192-202
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- (2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related pathway intermediate p-coumaric acid, which is an important factor for efficient production. Here, we first optimized the (2S)-naringenin biosynthetic pathway by alleviating the bottleneck downstream of p-coumaric acid and increasing malonyl-CoA supply, which improved (2S)-naringenin production but significant accumulation of p-coumaric acid still existed extracellularly. We thus established a dual dynamic control system through combining a malonyl-CoA biosensor regulator and an RNAi strategy, to autonomously control the synthesis of p-coumaric acid with the supply of malonyl-CoA. Furthermore, screening potential transporters led to identification of Pdr12 for improved (2S)-naringenin production and reduced accumulation of p-coumaric acid. Finally, a titer of 2.05 g/L (2S)-naringenin with negligible accumulation of p-coumaric acid was achieved in a fed batch fermentation. Our work highlights the importance of systematic control of pathway intermediates for efficient microbial production of plant natural products.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Natural products
- Intermediate distribution
- Synthetic biology
- Metabolic engineering
- Dynamic control
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Mao, Jiwei, 1990
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Tous Mohedano, M ...
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Fu, Jing, 1985
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Li, Xiaowei, 198 ...
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Liu, Quanli, 198 ...
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Nielsen, Jens B, ...
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visa fler...
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Siewers, Verena, ...
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Chen, Yun, 1978
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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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Metabolic Engine ...
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Chalmers tekniska högskola