Bioinformatics Approach for Metabolism Pathways Curation: Carbohydrate Metabolism and TCA Cycle in the Archaeon Sulfolobus solfataricus P2

Abstract

Background: Metabolic and genomic informatics integrations in organism-specific databases require comprehensive and intensive efforts. PathoLogic, a component of the Pathway Tools software package can create complete Pathway/Genome Databases (PGDBs) from genomic sequence and annotation files for any organism. This tool can predict the metabolic pathways using MetaCyc as a reference knowledge base. This work aimed to apply a bioinformatics approach to curate a PGDB created for the Crenarchaeon Sulfolobus solfataricus P2. This archaeon grows optimally at 80o C and pH 2-4. The complete genome of S. solfataricus P2 was released in 2001. Created PGDBs often need manual curations to fill in the metabolic gaps that the software failed to detect. Methods: We used Pathway Tools to create the PGDB for the Sulfolobus solfataricus P2. Bioinformatics curation for carbohydrate metabolism pathway (Entner-Doudoroff “ED”) and TCA cycle was carried out. Literature search as well as homology-, orthology- and context-based protein function prediction methods were followed for this curation using the Editors component of the Pathway Tools program. Results: Curation modified the number of the pathways in the database by adding extra pathways that have not been detected by the PathoLogic. New pathways such as semi-phosphorylated ED and a new variation of the TCA cycle were added to the PGDB of S. solfataricus P2. Filling in the metabolic holes (missing enzymes) in the pathways under study was also involved in the curation process. Conclusion: The bioinformatics curation of the PGDB of S. solfataricus P2 improved the database that can serve as a reference knowledge base for genomic annotations and metabolic pathway reconstructions of other organisms especially the closely related Archaea.