Metabolic Modeling of Streptococcus mutans Reveals Complex Nutrient Requirements of an Oral Pathogen.

is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). To better understand the metabolism of on a systematic level, we manually constructed a genome-scale metabolic model of the type strain UA159. The model, called iSMU, contains 675 reactions involving 429 metabolites and the products of 493 genes. We validated iSMU by comparing simulations with growth experiments in defined medium. The model simulations matched experimental results for 17 of 18 carbon source utilization assays and 47 of 49 nutrient depletion assays. We also simulated the effects of single gene deletions. The model's predictions agreed with 78.1% and 84.4% of the gene essentiality predictions from two experimental data sets. Our manually curated model is more accurate than models generated from automated reconstruction pipelines and more complete than other manually curated models. We used iSMU to generate hypotheses about the metabolic network. Subsequent genetic experiments confirmed that (i) catabolizes sorbitol via a sorbitol-6-phosphate 2-dehydrogenase (SMU_308) and (ii) the Leloir pathway is required for growth on complex carbohydrates such as raffinose. We believe the iSMU model is an important resource for understanding the metabolism of and guiding future experiments. Tooth decay is the most prevalent chronic disease in the United States. Decay is caused by the bacterium , an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of to systematically investigate how the bacterium grows. The model provides a valuable resource for understanding and targeting ' ability to outcompete other species in the oral microbiome.