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

Shuying Gu; Zhen Zhao; Yonghong Yao; Jingen Li; Chaoguang Tian

doi:10.3389/fbioe.2021.820507

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

Front Bioeng Biotechnol. 2022 Jan 19:9:820507. doi: 10.3389/fbioe.2021.820507. eCollection 2021.

Authors

Shuying Gu^{1

2

3}, Zhen Zhao^{1

2

3}, Yonghong Yao^{1

2}, Jingen Li^{1

2}, Chaoguang Tian^{1

2}

Affiliations

¹ Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
² National Technology Innovation Center of Synthetic Biology, Tianjin, China.
³ University of Chinese Academy of Sciences, Beijing, China.

Abstract

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 a-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 in vitro. Then, this synthetic pathway was functionally constructed in cellulolytic thermophilic fungus Myceliophthora thermophila. 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.

Keywords: Myceliophthora thermophila; a-keto decarboxylase; malonic acid; metabolic engineering; oxaloacetic acid.