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Formaldehyde formation in the glycine cleavage system and its use for an aldolase-based biosynthesis of 1,3-prodanediol
Citation Link: https://doi.org/10.15480/882.2791
Publikationstyp
Journal Article
Date Issued
2020-05-14
Sprache
English
Author(s)
Institut
TORE-DOI
TORE-URI
Volume
14
Issue
1
Article Number
15
Citation
Journal of Biological Engineering 1 (14): 15 (2020-05-14)
Publisher DOI
Scopus ID
Publisher
Springer
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.
Subjects
1,3- propanediol
5,10-CH -THF 2
Formaldehyde
Glycine cleavage system
DDC Class
600: Technik
More Funding Information
This work is financially supported by the Beijing Advanced Innovation Center for Soft Matter Science and Engineering.
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