Viral lysis and protistan grazing are thought to be the major processes leading to microbial mortality in aquatic environments and thus regulate community diversity and biogeochemical cycling characteristics. Here, we studied nutrient cycling and bacterial responses to cyanophage-mediated photoautotroph lysis and ciliate predation in a model Synechococcus-heterotroph co-culture system. Both viral lysis and Euplotes grazing facilitated the transformation of organic carbon from biomass to dissolved organic matter with convention efficiencies of 20%-26%. The accumulation of ammonium after the addition of phages and ciliates suggested the importance of recycled NH4+ occurred in the interactions between Synechococcus growth and heterotrophic bacterial metabolism of photosynthate. The slower efficiency of P mineralization compared to N (primarily ammonium) indicated that P-containing organic matter was primarily integrated into bacterial biomass rather than being remineralized into inorganic phosphate under C-rich conditions. In the cyanophage addition treatment, both Fluviicola and Alteromonas exhibited rapid positive responses to Synechococcus lysing, while Marivita exhibited an apparent negative response. Further, the addition of Euplotes altered the incubation system from a Synechococcus-driven phycosphere to a ciliate-remodelled zoosphere that primarily constituted grazing-resistant bacteria and Euplotes symbionts. Top-down controls increased co-culture system diversity and resulted in a preference for free-living lifestyles of dominant populations, which was accompanied by the transfer of matter and energy. Our results indicate top-down control was particularly important for organic matter redistribution and inorganic nutrient regeneration between photoautotrophs and heterotrophs, and altered bacterial lifestyles. This study consequently sheds light on marine biogeochemical cycling and the interaction networks within these dynamic ecosystems.