Shortening electron transfer distance to enhance chemicals and electric energy production in Escherichia coli

Abstract

Intracellular electron abundance affects the efficiency of biosynthetic pathways in microbial cell factories. However, regulating electron transfer efficiency to change intracellular electron abundance is challenging. Herein, we aimed to improve the electron transfer efficiency by shortening electron transfer distance using two systems: an extracellular electron transfer system (EET) and a light-driven intracellular electron regeneration system (ERS). The EET involved reconstructing an efficient electron transfer pathway (AEC4) and using periplasmic and biofilm engineering to improve its efficiency, whereas the ERS involved developing a biologically self-synthetic photosynthetic biohybrid system and using protein cage engineering to enhance its efficiency. As a proof of concept, the EET was implemented using a dynamic AND logic gate to increase the α-ketoglutarate titer to 30.4 g/L and the power density to 561.5 mW/m2 in microbial fuel cells. In a 5 L fermenter, the titer and productivity of α-ketoglutarate reached 67.7 g/L and 1.88 g/L/h, respectively. The ERS was manipulated using a chemo-optogenetic AND logic gate to increase the adipate titer to 43.1 g/L in a 5 L fermenter. Overall, our results provide a potential way to shorten electron transfer distance for the efficient production of valuable chemicals and electric energy.