iSMU

iSMU models the genome-scale metabolism of Streptococcus mutans UA159 to elucidate nutrient requirements and predict metabolic phenotypes.

Key Features:

• Comprehensive coverage: The model comprises 675 metabolic reactions, 429 metabolites, and the products of 493 genes representing S. mutans UA159 metabolism.
• Validation against experimental data: Growth simulations matched 17 out of 18 carbon source utilization assays and 47 out of 49 nutrient depletion assays in defined media.
• Gene essentiality predictions: Simulated single-gene deletions agreed with experimental gene essentiality data at 78.1% and 84.4% for two independent datasets.
• Manual curation: The reconstruction was manually curated and demonstrated improved accuracy and completeness relative to automated reconstruction pipelines.

Scientific Applications:

• Hypothesis generation: Enabled predictions such as sorbitol catabolism via sorbitol-6-phosphate 2-dehydrogenase (SMU_308) and dependence on the Leloir pathway for growth on raffinose.
• Experimental guidance: Guides experimental investigation of metabolic pathways and potential therapeutic targets related to lactic acid production and acid tolerance in S. mutans.

Methodology:

iSMU was constructed by manual curation and evaluated using simulations, including growth phenotype simulations and single-gene deletion analyses validated against carbon source and nutrient depletion assays, and compared to automated reconstructions.