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Engineering yeast m...
Engineering yeast mitochondrial metabolism for 3-hydroxypropionate production
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- Zhang, Yiming, 1986 (författare)
- Beijing University of Chemical Technology
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- Su, Mo (författare)
- Beijing University of Chemical Technology
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- Chen, Yu, 1990 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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visa fler...
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- Wang, Zheng (författare)
- Beijing University of Chemical Technology
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- Nielsen, Jens B, 1962 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology,Beijing University of Chemical Technology,BioInnovation Institute (BII)
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- Liu, Zihe, 1984 (författare)
- Beijing University of Chemical Technology
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visa färre...
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Biotechnology for Biofuels and Bioproducts. - 2731-3654. ; 16:1
- 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
- Background: With unique physiochemical environments in subcellular organelles, there has been growing interest in harnessing yeast organelles for bioproduct synthesis. Among these organelles, the yeast mitochondrion has been found to be an attractive compartment for production of terpenoids and branched-chain alcohols, which could be credited to the abundant supply of acetyl-CoA, ATP and cofactors. In this study we explored the mitochondrial potential for production of 3-hydroxypropionate (3-HP) and performed the cofactor engineering and flux control at the acetyl-CoA node to maximize 3-HP synthesis. Results: Metabolic modeling suggested that the mitochondrion serves as a more suitable compartment for 3-HP synthesis via the malonyl-CoA pathway than the cytosol, due to the opportunity to obtain a higher maximum yield and a lower oxygen consumption. With the malonyl-CoA reductase (MCR) targeted into the mitochondria, the 3-HP production increased to 0.27 g/L compared with 0.09 g/L with MCR expressed in the cytosol. With enhanced expression of dissected MCR enzymes, the titer reached to 4.42 g/L, comparable to the highest titer achieved in the cytosol so far. Then, the mitochondrial NADPH supply was optimized by overexpressing POS5 and IDP1, which resulted in an increase in the 3-HP titer to 5.11 g/L. Furthermore, with induced expression of an ACC1 mutant in the mitochondria, the final 3-HP production reached 6.16 g/L in shake flask fermentations. The constructed strain was then evaluated in fed-batch fermentations, and produced 71.09 g/L 3-HP with a productivity of 0.71 g/L/h and a yield on glucose of 0.23 g/g. Conclusions: In this study, the yeast mitochondrion is reported as an attractive compartment for 3-HP production. The final 3-HP titer of 71.09 g/L with a productivity of 0.71 g/L/h was achieved in fed-batch fermentations, representing the highest titer reported for Saccharomyces cerevisiae so far, that demonstrated the potential of recruiting the yeast mitochondria for further development of cell factories.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Bioprocessteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Bioprocess Technology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Biokatalys och enzymteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Biocatalysis and Enzyme Technology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Annan industriell bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Other Industrial Biotechnology (hsv//eng)
Nyckelord
- Acetyl-CoA carboxylase
- Malonyl-CoA reductase
- 3-Hydroxypropionate
- Redox factor engineering
- Yeast mitochondrion
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Zhang, Yiming, 1 ...
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Su, Mo
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Chen, Yu, 1990
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Wang, Zheng
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Nielsen, Jens B, ...
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Liu, Zihe, 1984
- Om ämnet
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- TEKNIK OCH TEKNOLOGIER
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TEKNIK OCH TEKNO ...
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och Industriell biot ...
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och Bioprocessteknik
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- TEKNIK OCH TEKNOLOGIER
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TEKNIK OCH TEKNO ...
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och Industriell biot ...
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och Biokatalys och e ...
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- TEKNIK OCH TEKNOLOGIER
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TEKNIK OCH TEKNO ...
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och Industriell biot ...
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Chalmers tekniska högskola