TY - JOUR A1 - Öppinger, Christian Manfred A1 - Kremp, Florian A1 - Müller, Volker T1 - Is reduced ferredoxin the physiological electron donor for MetVF-type methylenetetrahydrofolate reductases in acetogenesis? A hypothesis T2 - International microbiology N2 - The methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme in acetogenic CO2 fixation. The MetVF-type enzyme has been purified from four different species and the physiological electron donor was hypothesized to be reduced ferredoxin. We have purified the MTHFR from Clostridium ljungdahlii to apparent homogeneity. It is a dimer consisting of two of MetVF heterodimers, has 14.9 ± 0.2 mol iron per mol enzyme, 16.2 ± 1.0 mol acid-labile sulfur per mol enzyme, and contains 1.87 mol FMN per mol dimeric heterodimer. NADH and NADPH were not used as electron donor, but reduced ferredoxin was. Based on the published electron carrier specificities for Clostridium formicoaceticum, Thermoanaerobacter kivui, Eubacterium callanderi, and Clostridium aceticum, we provide evidence using metabolic models that reduced ferredoxin cannot be the physiological electron donor in vivo, since growth by acetogenesis from H2 + CO2 has a negative ATP yield. We discuss the possible basis for the discrepancy between in vitro and in vivo functions and present a model how the MetVF-type MTHFR can be incorporated into the metabolism, leading to a positive ATP yield. This model is also applicable to acetogenesis from other substrates and proves to be feasible also to the Ech-containing acetogen T. kivui as well as to methanol metabolism in E. callanderi. KW - Methylene-tetrahydrofolate reductase KW - MetVF KW - Acetogen KW - Wood-Ljungdahl pathway KW - Acetogenesis Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62814 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-628141 SN - 1618-1905 N1 - Open Access funding enabled and organized by Projekt DEAL. We are indebted to the Deutsche Forschungsgemeinschaft (DFG) for funding. VL - 25.2021 IS - 1 SP - 75 EP - 88 PB - Spanish Soc. for Microbiology CY - Madrid ER -