Phototrophic sulfur bacteria are important for primary production in many stratified lakes. In Lake Cadagno, these bacteria greatly contribute to the total primary production with high values of CO2 fixation both in the presence and absence of light. The small-celled PSB Candidatus “Thiodictyon syntrophicum” Cad16T was the strongest CO2 assimilator and used as model organism. The draft genome sequence of strain Cad16T revealed the presence of two RuBisCO genes (cbbL and cbbM), which were deferentially expressed. 2D-DIGE analysis showed the presence of 23 protein spots up-regulated in the light, and 17 in the dark. Among the 23 protein spots that were up-regulated in the light, three are involved in the storage mechanism that produces granules of poly(3-hydroxybutyrate) from an excess of reducing power and carbon compounds. Among the 17 protein spots up-regulated in the dark, three were found to be part of the autotrophic dicarboxylate-hydroxybutyrate (DC/HB) cycle.