RxnCluster: A Web-Based Tool for Exploring Reaction Clusters Leading to Target Molecules by Digitalizing Typical...

Biosynthetic pathways for producing target molecules can be regarded as series of sequential reactions that can also be digitalized as typical biosynthetic patterns (reaction rule clusters) for producing analogs. Conventional methods for pathway design in silico consider only reaction rules with a single step, which neglect the more efficient synthetic strategies crossing multiple steps. The structure of a molecule is topological and can be divided into multiple substructures; different molecules with one or more identical substructure fragments may have similar biosynthetic strategies. Here, based on the concept of gene clusters, we constructed a user-friendly platform (RxnCluster) by digitalizing the typical biosynthetic patterns for the first time. RxnCluster contains 14,378 biosynthetic patterns (reaction rule clusters) covering 37,317 reaction combinations (reaction clusters) whose numbers of steps vary from 1 to 4. According to the results, this platform can identify the reaction clusters in various numbers of steps, which are consistent with the experimental results obtained in wet laboratories. In addition, it can identify other novel reaction clusters that have not yet been reported, which will pave the way toward pathway mining for molecule biosynthesis via different strategies. RxnCluster is available at http://design.rxnfinder.org/rxncluster/.