Categorization of growth substrates based on NADPH demand and requirement for PntAB under photosynthetic conditions. (A) R. sphaeroides growth on glucose via the Entner-Doudoroff pathway includes the NADPH-generating glucose-6-phosphate (G6P) dehydrogenase enzyme (Zwf), which supports normal photosynthetic growth even in the absence of PntAB. (B) R. sphaeroides growth on acetate is predicted to occur via the ethylmalonyl-CoA (EM-CoA) pathway, involving oxidation of 2 molecules of NADPH per 3 molecules of acetyl-CoA (A-CoA) consumed . Note that a third molecule of A-CoA used up in later steps of the EM-CoA pathway is not depicted in this illustration. (C) During photosynthetic growth on substrates that do not directly produce NADPH (e.g. succinate), PntAB is required. In some cases, after a long lag period, cells adapt and grow photosynthetically albeit at a slower growth rate (17.2 ± 0.56 hrs compared to 7.53 ± 0.56 hrs for wild type cells). Abbreviations: AA-CoA – acetoacetyl-CoA; 3HB-CoA – 3-hydroxy butyryl-CoA; Cr-CoA – crotonyl-CoA; 6PGL – phosphoglucono-δ-lactone.