Proteoliposomes containing ATPase as microreactors to mimic microbial metabolism for bioenergy synthesis

Learning and imitating the inherent metabolic pathways of organisms in nature has emerged as a crucial approach to achieve artificial biomimetic synthesis of Adenosine triphosphate (ATP). We have constructed a biomimetic microreactor inspired by the ethanol metabolism pathway in microorganisms. The alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) loaded in the microreactor can catalyze the cascade reaction of ethanol to acetic acid. This proton-producing reaction is spatially coupled with the ATP synthase embedded in proteoliposomes, establishing a transmembrane proton gradient that drives ATP synthase to synthesize ATP. The generated ATP concentration can reach up to 6.3 μM within 30 min, which is rather high. The microreactors effectively reconstruct the core step of acetic fermentation process to convert chemical energy into bioenergy. This work demonstrates a novel and efficient route to transform low-value, readily available basic chemical products into universal biological energy carrier ATP, bypassing the need for intricate metabolic networks. Such a design provides a foundational model for understanding and engineering cellular metabolism.