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In Vivo Rate of Formaldehyde Condensation with Tetrahydrofolate

  • Formaldehyde is a highly reactive compound that participates in multiple spontaneous reactions, but these are mostly deleterious and damage cellular components. In contrast, the spontaneous condensation of formaldehyde with tetrahydrofolate (THF) has been proposed to contribute to the assimilation of this intermediate during growth on C1 carbon sources such as methanol. However, the in vivo rate of this condensation reaction is unknown and its possible contribution to growth remains elusive. Here, we used microbial platforms to assess the rate of this condensation in the cellular environment. We constructed Escherichia coli strains lacking the enzymes that naturally produce 5,10-methylene-THF. These strains were able to grow on minimal medium only when equipped with a sarcosine (N-methyl-glycine) oxidation pathway that sustained a high cellular concentration of formaldehyde, which spontaneously reacts with THF to produce 5,10-methylene-THF. We used flux balance analysis to derive the rate of the spontaneous condensation from theFormaldehyde is a highly reactive compound that participates in multiple spontaneous reactions, but these are mostly deleterious and damage cellular components. In contrast, the spontaneous condensation of formaldehyde with tetrahydrofolate (THF) has been proposed to contribute to the assimilation of this intermediate during growth on C1 carbon sources such as methanol. However, the in vivo rate of this condensation reaction is unknown and its possible contribution to growth remains elusive. Here, we used microbial platforms to assess the rate of this condensation in the cellular environment. We constructed Escherichia coli strains lacking the enzymes that naturally produce 5,10-methylene-THF. These strains were able to grow on minimal medium only when equipped with a sarcosine (N-methyl-glycine) oxidation pathway that sustained a high cellular concentration of formaldehyde, which spontaneously reacts with THF to produce 5,10-methylene-THF. We used flux balance analysis to derive the rate of the spontaneous condensation from the observed growth rate. According to this, we calculated that a microorganism obtaining its entire biomass via the spontaneous condensation of formaldehyde with THF would have a doubling time of more than three weeks. Hence, this spontaneous reaction is unlikely to serve as an effective route for formaldehyde assimilation.zeige mehrzeige weniger

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Metadaten
Verfasserangaben:Hai HeORCiD, Elad NoorORCiD, Perla A. Ramos-Parra, Liliana E. García-ValenciaORCiD, Jenelle A. Patterson, Rocío I. Díaz de la GarzaORCiD, Andrew D. HansonORCiD, Arren Bar-EvenORCiD
URN:urn:nbn:de:kobv:517-opus4-476472
DOI:https://doi.org/10.25932/publishup-47647
ISSN:1866-8372
Titel des übergeordneten Werks (Deutsch):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
Schriftenreihe (Bandnummer):Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (998)
Publikationstyp:Postprint
Sprache:Englisch
Datum der Erstveröffentlichung:16.09.2020
Erscheinungsjahr:2020
Veröffentlichende Institution:Universität Potsdam
Datum der Freischaltung:16.09.2020
Freies Schlagwort / Tag:auxotrophy; one-carbon metabolism; phenotypic phase plane; serine cycle; spontaneous reaction
Ausgabe:998
Seitenanzahl:17
Quelle:Metabolites 10 (2020) 2, 65 DOI:10.3390/metabo10020065
Organisationseinheiten:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
DDC-Klassifikation:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Peer Review:Referiert
Publikationsweg:Open Access / Green Open-Access
Lizenz (Deutsch):License LogoCC-BY - Namensnennung 4.0 International
Externe Anmerkung:Bibliographieeintrag der Originalveröffentlichung/Quelle
Externe Anmerkung:This article is part of this cumulative dissertation
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