Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast
Journal article, 2024
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.
Author
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
Shenzhen Institute of Advanced Technology
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
Tianjin Institute of Industrial Biotechnology
Jianye Xia
Tianjin Institute of Industrial Biotechnology
Shuobo Shi
Beijing University of Chemical Technology
Tianwei Tan
Beijing University of Chemical Technology
Jens B Nielsen
Chalmers, Life Sciences, Systems and Synthetic Biology
BioInnovation Institute
Beijing University of Chemical Technology
Yun Chen
Novo Nordisk Foundation
Chalmers, Life Sciences, Systems and Synthetic Biology
Zihe Liu
Beijing University of Chemical Technology
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 15 1 1591Subject Categories
Chemical Process Engineering
Bioprocess Technology
DOI
10.1038/s41467-024-45557-9
PubMed
38383540