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

Ning Qin, Lingyun Li, Xiaozhen Wan, Xu Ji, Yu Chen, Chaokun Li, Ping Liu, Yijie Zhang, Weijie Yang, Junfeng Jiang, Jianye Xia, Shuobo Shi, Tianwei Tan, Jens Nielsen (), Yun Chen () and Zihe Liu ()
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Ning Qin: Beijing University of Chemical Technology
Lingyun Li: Beijing University of Chemical Technology
Xiaozhen Wan: Beijing University of Chemical Technology
Xu Ji: Beijing University of Chemical Technology
Yu Chen: Chinese Academy of Sciences
Chaokun Li: University of Helsinki
Ping Liu: Beijing University of Chemical Technology
Yijie Zhang: Beijing University of Chemical Technology
Weijie Yang: Beijing University of Chemical Technology
Junfeng Jiang: Chinese Academy of Sciences
Jianye Xia: Chinese Academy of Sciences
Shuobo Shi: Beijing University of Chemical Technology
Tianwei Tan: Beijing University of Chemical Technology
Jens Nielsen: Beijing University of Chemical Technology
Yun Chen: Chalmers University of Technology
Zihe Liu: Beijing University of Chemical Technology

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 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 CO2, 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 CO2 fixation strategies pave the way for CO2 being used as the sole carbon source.

Date: 2024
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DOI: 10.1038/s41467-024-45557-9

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