AUTHOR=Gu Shuying , Zhao Zhen , Yao Yonghong , Li Jingen , Tian Chaoguang 

TITLE=Designing and Constructing a Novel Artificial Pathway for Malonic Acid Production Biologically

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.820507

DOI=10.3389/fbioe.2021.820507

ISSN=2296-4185

ABSTRACT=<p>Malonic acid is used as a common component of many products and processes in the pharmaceutical and cosmetic industries. Here, we designed a novel artificial synthetic pathway of malonic acid, in which oxaloacetate, an intermediate of cytoplasmic reductive tricarboxylic acid (rTCA) pathway, is converted to malonic semialdehyde and then to malonic acid, sequentially catalyzed by <italic>a</italic>-keto decarboxylase and malonic semialdehyde dehydrogenase. After the systematic screening, we discovered the enzyme oxaloacetate decarboxylase Mdc, catalyzing the first step of the artificially designed pathway <italic>in vitro</italic>. Then, this synthetic pathway was functionally constructed in cellulolytic thermophilic fungus <italic>Myceliophthora thermophila</italic>. After enhancement of glucose uptake, the titer of malonic acid achieved 42.5 mg/L. This study presents a novel biological pathway for producing malonic acid from renewable resources in the future.</p>