The only nutrients from which the streptococci can obtain sufficient energy to support growth and cell division are carbohydrates, which are oxidized to pyruvate via glycolysis. The R6 strain of S. pneumoniae is able to grow at the expense of the monosaccharides, glucose, mannose, fructose and galactose; the disaccharides, sucrose, lactose, trehalose, maltose and cellobiose; the trisaccharide, raffinose, and the fructose oligosaccharide, inulin. Genes were identified that encode enzymes necessary for transport of these substrates into the cell and for their subsequent conversion to an intermediate in glycolysis. Based on genes and operons identified, the following predictions can be made. Mannose and glucose likely enter the cell as the 6-carbon phosphate, via EII^man, followed by conversion to fructose-6-phosphate via the activity of phosphomannose isomerase and phosphoglucose isomerase, respectively. An EII^fru transports fructose into the cell as fructose-6-phosphate. Galactose is transported by an ABC transporter, and subsequently enters the glycolytis under the activity of the Leloir pathway enzymes. Lactose, sucrose and trehalose are each transported by its respective sugar-specific EII. Intracellular lactose-phosphate is hydrolyzed to glucose and galactose-6-phosphate by phospho-b -galactosidase. The glucose is phosphorylated in the 6-carbon position by glucokinase, and the galactose moiety is further converted to triose-phosphate by enzymes of the tagatose pathway. Sucrose-phosphate is split by sucrose-phosphate hydrolase to glucose-6-phosphate and fructose, the latter being phosphorylated in the 6-carbon position by fructokinase. Although an EII^tre gene was identified, no gene encoding an enzyme the might be expected to hydrolyze the trehalose phosphate product was found. A cellobiose-specific EII was identified, and the intracellular sugar phosphate is split by a b -glucosidase, yielding glucose and glucose-6 phosphate. Maltose and maltodextrins are transported into the cell via an ABC transporter, and the glucose moieties that are released via the activity of dextran glucosidase, and the glucose product of b -glucosidase, are phosphorylated by glucokinase. Metabolism of raffinose is mediated by the raffinose (multiple sugar metabolism) regulon, which encodes an ABC transport complex for entry of raffinose into the cell, an a -galactosidase to hydrolyze the trisaccharide to galactose and sucrose, and a sucrose phosphorylase, which catalizes the hydrolysis of sucrose to glucose-6-phosphate and fructose. The galactose and fructose moeities are acted on via the enzymes of the Leloir pathway and fructokinase, respectively. No genes that might encode inulin transport and hydrolytic enzymes were identified. Although complete pathways for the metabolism of L-fucose and mannitol appeared to be encoded, neither was utilized by strain R6. Several additional putative EII components, and potential carbohydrate ABC transporters were identified, but it was not possible, without phenotypic data, to attribute the transport of a specific sugar to any of these.

With few exceptions, the lactic acid bacteria obtain their metabolic energy exclusively from the fermentation of carbohydrates. S. pneumoniae R6, as expected, encodes all genes necessary for the oxidation of carbohydrates to pyruvate via glycolysis, and would be expected to reoxidize most, if not all, of the NADH produced by the reduction of pyruvic acid to lactic acid. The genome of R6 does contain genes for the synthesis of phosphotransacetylase, acetokinase and NADH oxidase, which would allow it to convert pyruvate to acetate, with concomitant production of an additional ATP, and the reoxidation of NADH. Since fermentation is the least energy efficient of oxidative processes, it is not surprising that seven of the carbohydrates that serve as carbon and energy sources for R6 are transported into the cell via the PEP-dependent phosphotransferase system, rather than by a less efficient ABC transporter. No genes were found that might encode for cation antiport of these substrates, although several amino acid/cationic symport systems were identified. All genes necessary for synthesis of the major ATPase of lactic acid bacteria, the F_OF₁-ATPase, were present. This proton pump works at the expense of ATP, but can also serve as an ATP synthase, as well the major regulator of intracellular pH among lactic acid bacteria. Genes required for a complete electron transport chain that might be associated with either aerobic or anaerobic respiration were not found. Furthermore, although no lactic acid bacterial species encodes a complete TCA cycle, the R6 genome contained none of genes for this aerobic oxidative pathway.

The graphic below shows ATP production from fermentation of carbohydrates imported via the PTS system. The blue numbers and ATPs to the right of the carbohydrate species are the number of molecules generated and consumed from disaccharide catabolism. Blue numbers, and ATPs to the left of carbohydrate species are the number of molecules generated or consumed from monosaccharide fermentation.