Formaldehyde formation in the glycine cleavage system and its use for an aldolase-based biosynthesis of 1,3-prodanediol

Formaldehyde formation in the glycine cleavage system and its use for an aldolase-based biosynthesis of 1,3-prodanediol

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Abstract 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) Bath and Body 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 Jumbo OFC (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.