Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast

CO 2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO 2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the p...

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Veröffentlicht in:Nature communications 2024-02, Vol.15 (1), p.1591-1591, Article 1591
Hauptverfasser: Qin, Ning, Li, Lingyun, Wan, Xiaozhen, Ji, Xu, Chen, Yu, Li, Chaokun, Liu, Ping, Zhang, Yijie, Yang, Weijie, Jiang, Junfeng, Xia, Jianye, Shi, Shuobo, Tan, Tianwei, Nielsen, Jens, Chen, Yun, Liu, Zihe
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Sprache:eng
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Zusammenfassung:CO 2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO 2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO 2 , restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO 2 fixation strategies pave the way for CO 2 being used as the sole carbon source. CO 2 fixation plays an important role to make bioproduction cost competitive. Here, the authors take 3-hydroxypropionic acid as an example to showcase how to achieve high carbon yield production through increasing the accessible bicarbonate, minimizing native CO 2 release and avoiding carbon waste.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45557-9