RAVEN Toolbox

The RAVEN Toolbox, specifically its version 2.0, represents a significant advancement in genome-scale metabolic model (GEM) reconstruction, curation, and constraint-based modeling and simulation. Developed for use within the MATLAB environment, RAVEN 2.0 introduces major enhancements to support and streamline the processes involved in metabolic network analysis.

Key features of RAVEN 2.0 include: 1. De novo Reconstruction: Utilizing the MetaCyc pathway database, RAVEN 2.0 allows for the automated de novo reconstruction of GEMs, broadening the scope of organisms and metabolic pathways that can be analyzed.
2. Redesigned KEGG-based Reconstruction Pipeline: The pipeline for constructing GEMs based on information from the KEGG database has been redesigned for improved efficiency and accuracy.
3. Convergence of Reconstructions: This version facilitates the integration of reconstructions from various sources, ensuring a more comprehensive and unified model representation.
4. Enhanced Performance and Usability: RAVEN 2.0 boasts improved performance metrics and user-friendly features, making it more accessible to researchers.
5. Compatibility with COBRA Toolbox: Ensuring interoperability with the widely used COBRA Toolbox, RAVEN 2.0 supports a seamless workflow for users engaged in constraint-based modeling.

The capabilities of RAVEN 2.0 are demonstrated through the de novo reconstruction of GEMs for Streptomyces coelicolor, an antibiotic-producing bacterium. This application showcases how RAVEN 2.0 can effectively capture the complexity of a high-quality, manually curated model (iMK1208) through automated processes. The further de novo reconstruction, used to curate the iMK1208 model into Sco4, exemplifies the tool's potential for enhancing existing models. Sco4 emerges as the most comprehensive GEM of S. coelicolor, with extended coverage of both primary and secondary metabolism. The expanded metabolic coverage opens new avenues for using Sco4 in predicting genome editing targets for optimized production of secondary metabolites.