Coupled extracellular and intracellular electron transfer chains in methanogens: Mechanisms, energy conservation, and...

Syntrophic interaction between acetogens and methanogens is the key to address thermodynamic challenges in anaerobic digestion (AD), the strengthening of which can benefit microbial energy production and their application in environmental remediation. Metabolic activities occurring during the syntrophic interactions primarily involve extracellular to intracellular electron transfers, facilitating the optimum exchange and utilization of energy. This occurs extracellularly through mediated interspecies electron transfer (MIET) and direct interspecies electron transfer (DIET), while in methanogens, electron transport phosphorylation (ETP) as a membrane-based process and flavin-based electron bifurcation (FBEB) for intracellular electron transfer are the main pathways. Despite the extensive efforts to understand extracellular and intracellular electron transfer, little is known about their coupling in methanogens. This review examines the mechanisms of MIET, DIET, and FBEB-based electron transfers, highlighting the molecular mechanisms facilitating the coupling of extracellular and intracellular electron transfers. It also analyzes the optimized electron transfer and energy conservation strategies. The underscored DIET and FBEB-coupled electron transfer chain presents a novel avenue for enhancing the adaptability and efficiency of AD. This review proposes the ingenious idea to link the intracellular and extracellular electron transfer chains, and provides potential strategies to enhance AD that can be applied to wastewater treatment and ecosystem protection technologies.