RetroRules

RetroRules provides a comprehensive set of stereochemistry-aware reaction rules for retrosynthesis-based metabolic pathway discovery and metabolic engineering.

Key Features:

• Reaction rule collection: Over 400,000 stereochemistry-aware reaction rules extracted from public databases.
• Chemical encoding: Rules expressed in the community-standard SMARTS (SMIRKS) format.
• Multi-level specificity: Multiple levels of specificity representing the atomic environment around the reaction center.
• Enzyme promiscuity modeling: Rules enable prediction of de novo reactions facilitated by promiscuous enzymes and expansion of natural chemical diversity.
• Retrosynthesis support: Rules support enumeration of biosynthetic routes that connect target molecules to precursors in retrosynthesis workflows.
• Tool compatibility: Rules provided for use with open-source cheminformatics tools such as RDKit and for integration with retrosynthetic codes like RetroPath2.0.

Scientific Applications:

• Metabolic pathway discovery: Enumerating candidate biosynthetic pathways from target compounds to precursors.
• Metabolic engineering: Designing and assessing de novo metabolic routes for production of target molecules.
• Synthetic biology: Enabling discovery of de novo pathways informed by predicted promiscuous reactions.
• Systems biology: Investigating underground metabolism arising from enzyme promiscuity.
• Retrosynthesis workflows: Automating retrosynthetic enumeration of biosynthetic routes using reaction rules.

Methodology:

Reaction rules were extracted from public databases and encoded in SMARTS (SMIRKS) with stereochemistry awareness; each rule is represented at multiple levels of atomic-environment specificity and provided for use with RDKit and RetroPath2.0.