BACKGROUND: The capability of cyanobacteria to convert carbon dioxide into carbohydrates offers a promising carbon-neutral energy solution. Unfortunately, the lifespan of cyanobacteria based photoelectrochemical cells is poor because discharge current drops to zero within days. The primary factor that limits lifespan was believed to be the toxicity of an artificial mediator that extracts electrons from cyanoacteria to electrode. It is critical to experimentally identify the true limiting factor such that we could prolong the lifespan for practical use. RESULTS: Systematic tests on cell physiology and current discharge were performed in autotrophic and heterotrophic conditions. Contrary to previous belief, results for cell viability, chlorophyll content and growth curve of Cyanobacterium Synechocystis PCC 6714 under continuous vitamin K-3-mediated current discharge did not exhibit any toxic effect. The role of glucose was then investigated. Surprisingly, discharge current dropped to zero although there was significant intracellular glycogen (2.5 x 10(-10) mg cell(-1)). Further tests of current response to the addition of exogenous glucose suggest the regulatory role of glucose on cyanobacterial metabolism that is relevant to current generation. Furthermore, current generation in the light and dark conditions corroborates glucose as energy reserve. CONCLUSION: It is not mediator toxicity but the regulatory effect of glucose on the metabolism of cyanobacteria that limits the lifespan for current generation. Glucose functions in a dual role as energy reserve and regulatory molecule to modulate cyanobacterial metabolism related to current generation. (C) 2010 Society of Chemical Industry