Issue 12, 2021

A biosynthesis pathway for 3-hydroxypropionic acid production in genetically engineered Saccharomyces cerevisiae

Abstract

3-Hydroxypropionic acid (3-HP) is an emerging platform chemical, which can be used for the production of various value-added chemicals. The traditional chemical synthesis of 3-HP has some difficulties in meeting the new sustainable development goals. Accordingly, microbial cell factories offer a green and sustainable method for the biosynthesis of 3-HP. Herein, a novel oxaloacetate pathway was successfully established for 3-HP biosynthesis. Firstly, a 3-HP production module was designed and constructed in Saccharomyces cerevisiae by overexpressing pyruvate carboxylase, benzoylformate decarboxylase, and 3-hydroxyisobutyrate dehydrogenase. Secondly, promoter engineering was used to optimize the glc7 expression, which could regulate the dephosphorylation of hexokinase to enhance the cytoplasmic energy metabolism, resulting in a 74.4% increase in 3-HP titer. Furthermore, a quorum-sensing system was applied to regulate the ptc7 expression, which could control the dephosphorylation of citrate synthase and mitochondrial hydroxylase to enhance the mitochondrial energy metabolism, resulting in a 98.0% increase in 3-HP titer. Finally, to further improve the 3-HP production, dynamic control of dephosphorylation was achieved to optimize the cytoplasmic and mitochondrial energy metabolism, resulting in a 4.2-fold increase in 3-HP titer in a 5 L bioreactor. The final engineered strain, thTAM-47, produced 18.1 g L−1 3-HP, which is the highest level of 3-HP production in S. cerevisiae to date. This work showed the shortest pathway for 3-HP production using glucose as a substrate in S. cerevisiae at present. Also, this is the first report on improving the pathway efficiency of 3-HP biosynthesis using a dephosphorylation regulation strategy to increase the intracellular ATP level.

Graphical abstract: A biosynthesis pathway for 3-hydroxypropionic acid production in genetically engineered Saccharomyces cerevisiae

Supplementary files

Article information

Article type
Paper
Submitted
31 Dec 2020
Accepted
29 Apr 2021
First published
06 May 2021

Green Chem., 2021,23, 4502-4509

A biosynthesis pathway for 3-hydroxypropionic acid production in genetically engineered Saccharomyces cerevisiae

T. Tong, Z. Tao, X. Chen, C. Gao, H. Liu, X. Wang, G. Liu and L. Liu, Green Chem., 2021, 23, 4502 DOI: 10.1039/D0GC04431H

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