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Publisher DOI: 10.1186/s13036-020-00237-2
Title: Formaldehyde formation in the glycine cleavage system and its use for an aldolase-based biosynthesis of 1,3-prodanediol
Language: English
Authors: Xu, Yingying 
Meng, Hao 
Ren, Jie 
Zeng, An-Ping  
Keywords: 1,3- propanediol;5,10-CH -THF 2;Formaldehyde;Glycine cleavage system
Issue Date: 14-May-2020
Publisher: Springer
Source: Journal of Biological Engineering 1 (14): 15 (2020-05-14)
Journal or Series Name: Journal of biological engineering 
Abstract (english): Glycine cleavage system (GCS) occupies a key position in one-carbon (C1) metabolic pathway and receives great attention for the use of C1 carbons like formate and CO2 via synthetic biology. In this work, we demonstrate that formaldehyde exists as a substantial byproduct of the GCS reaction cycle. Three causes are identified for its formation. First, the principal one is the decomposition of N 5,N 10 -methylene-tetrahydrofolate (5,10-CH2-THF) to form formaldehyde and THF. Increasing the rate of glycine cleavage promotes the formation of 5,10-CH2-THF, thereby increasing the formaldehyde release rate. Next, formaldehyde can be produced in the GCS even in the absence of THF. The reason is that T-protein of the GCS can degrade methylamine-loaded H-protein (Hint) to formaldehyde and ammonia, accompanied with the formation of dihydrolipoyl H-protein (Hred), but the reaction rate is less than 0.16% of that in the presence of THF. Increasing T-protein concentration can speed up the release rate of formaldehyde by Hint. Finally, a certain amount of formaldehyde can be formed in the GCS due to oxidative degradation of THF. Based on a formaldehyde-dependent aldolase, we elaborated a glycine-based one carbon metabolic pathway for the biosynthesis of 1,3-propanediol (1,3-PDO) in vitro. This work provides quantitative data and mechanistic understanding of formaldehyde formation in the GCS and a new biosynthetic pathway of 1,3-PDO.
DOI: 10.15480/882.2791
ISSN: 1754-1611
Institute: Bioprozess- und Biosystemtechnik V-1 
Type: (wissenschaftlicher) Artikel
Funded by: This work is financially supported by the Beijing Advanced Innovation Center for Soft Matter Science and Engineering.
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