Cyclic adenosine monophosphate (cAMP) signaling reprograms extracellular electron transfer of Shewanella oneidensis.

Limited extracellular electron transfer (EET) efficiency constrains the electrocatalytic performance of Shewanella oneidensis MR-1. Although the c-type cytochrome (c-Cyts) network is essential for EET, its regulatory mechanisms remain incompletely understood. This study systematically compared the effects of overexpressing c-Cyts components versus cAMP receptor protein (CRP) modulation on EET efficiency in microbial fuel cells (MFCs). Overexpression of individual c-Cyts failed to enhance EET. In contrast, coexpression of CymA, CctA, and MtrCBA (strain CC-Mtr) increased the maximum power density to 0.29 W/m2, 29.5% higher than MR-1. This indicates that efficient EET requires synergistic activity of a transmembrane electron transfer chain. However, strain CC-Mtr exhibited impaired growth. By comparison, cAMP-CRP global regulation markedly upregulated genes involved in c-Cyts biosynthesis, cytochrome maturation, and anaerobic carbon metabolism. This strategy improved both the electron transfer chain and cellular growth. In the cyaC strain, where intracellular cAMP levels were 2.8-fold higher than in MR-1, the MFC current density reached 0.94 A/m², a 32.1% increase over the wild-type and 11.7% higher than strain CC-Mtr. These findings demonstrate that EET can be effectively enhanced by upregulating the full electron transport chain and cAMP-CRP mediated global regulation, offering a promising strategy for optimizing electron transfer in microbial electrosynthesis systems.