Recently, the researchers from the State Key Laboratory of Microbial Technology of Shandong University and Shanghai Jiao Tong University made a new progress in the field of microbial L-serine biosynthesis.
The paper entitled "Coupling between D-3-phosphoglycerate dehydrogenase and D-2-hydroxyglutarate dehydrogenase drives bacterial L-serine synthesis" was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS Plus, 2017, 114: E7574-E7582). Wen Zhang, the graduated PhD student of the State Key Laboratory of Microbial Technology, is the first author. Associate professor Gao Chao of the State Key Laboratory of Microbial Technology is the co-corresponding author.
L-Serine is a source of one-carbon units, and serves as a precursor for the biosynthesis of glycine, cysteine, tryptophan, and phospholipids. L-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by D-3-phosphoglycerate (D-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by D-3-PG dehydrogenase (SerA). According to the conventional view, D-3-PG dehydrogenation is driven through coupling with the reactions catalyzed by L-phosphoserine aminotransferase (SerC) and L-phosphoserine phosphatase (SerB) in L-serine synthesis. This study indicated that the coupled reactions between SerA, SerB and SerC are not thermodynamically favorable, and demonstrated that SerA catalyzes the coupled reaction between D-3-PG dehydrogenation and 2-KG reduction to D-2-HG. SerA combines the energetically favorable reaction of 2-ketoglutarate (2-KG) reduction to overcome the thermodynamic barrier of D-3-PG dehydrogenation and result in D-2-HG production. D-2-HG dehydrogenase (D2HGDH) converts D-2-HG back to 2-KG, re-entering the central metabolism. Although this study chose Pseudomonas as research subjects, it was revealed that the coupling between D2HGDH and SerA also takes place in eukaryotic microorganisms, animals, and plants.
Associate professor Gao Chao has been engaged for a long time in the microbial metabolic mechanism of 2-hydroxycarboxylic acid. In the past five years, he has published more than 20 articles in the Green Chem, ACS Chem Chem, J Bacteriol, Appl Environ Microbiol and other SCI journals. The above studies have been funded by the National Natural Science Foundation of China and Young Scholars Program of Shandong University.
Related links: http://www.pnas.org/content/114/36/E7574
Source: the State Key Laboratory of Microbial Technology of Shandong University
Written by: Ma Cuiqing
Edited by: Xie Tingting