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An aldolase-catalyzed new metabolic pathway for the assimilation of formaldehyde and methanol to synthesize 2-keto-4-hydroxybutyrate and 1,3-propanediol in Escherichia coli.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "An aldolase-catalyzed new metabolic pathway for the assimilation of formaldehyde and methanol to synthesize 2-keto-4-hydroxybutyrate and 1,3-propanediol in Escherichia coli."

Formaldehyde (HCHO) is an important intermediate in the metabolism of one-carbon (C1) compounds such as methanol, formate and methane. The ribulose monophosphate (RuMP) pathway is the mostly studied HCHO assimilation route and the 3-hexulose-6-phosphate synthase (Hps) plays an important role for HCHO fixation. In this study, we proposed and selected a pyruvate-dependent aldolase to channel HCHO into 2-keto-4-hydroxybutyrate as an important intermediate for biosynthesis. By combining this reaction with three further enzymes we demonstrated a pyruvate-based C1 metabolic pathway for biosynthesis of the appealing compound 1,3-propanediol (1,3-PDO). The novel pathway is first confirmed in vitro using HCHO and pyruvate as substrates. It is then demonstrated in vivo in E. coli for 1,3-PDO production from HCHO and methanol with glucose as a co-substrate. This de novo pathway has several decisive advantages over the known metabolic pathways for 1,3-
PDO:
1) C1 carbon is directly channeled into a precursor of 1,3-PDO; 2) the use of pyruvate as an acceptor of HCHO is glycerol-independent, circumventing thus the need of coenzyme B12 as cofactor for glycerol dehydration; 3) the pathway is much shorter and more simple than the recently proposed L-homoserine-dependent pathway, avoiding thus complicated regulations involving precursors for essential amino acids. In addition to proof-of-concept we further improved the host strain by deleting a gene (frmA) responsible for the conversion of HCHO to formate, thereby increasing the production of 1,3-PDO from 298.3 ± 11.4 mg/L to 508.3 ± 9.1 mg/L and from 3.8 mg/L to 32.7 ± 0.8 mg/L with HCHO and methanol as co-substrate of glucose fermentation, respectively. This work is the first study demonstrating a genetically engineered E. coli that can directly use HCHO or methanol for the synthesis of 2-keto-4-hydroxybutyrate and its further conversion to 1,3-PDO.

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This article was published in the following journal.

Name: ACS synthetic biology
ISSN: 2161-5063
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