Exploring Chemical Biosynthetic Design Space with Transform-MinER.
Transform-MinER (Transforming Molecules in Enzyme Reactions) is a web application facilitating the exploration of chemical biosynthetic space, guiding the user toward promising start points for enzyme design projects or directed evolution experiments. Two types of search are possible: Molecule Search allows a user to submit a source substrate enabling Transform-MinER to search for enzyme reactions acting on similar substrates, whereas Path Search additionally allows a user to submit a target molecule enabling Transform-MinER to search for a path of enzyme reactions acting on similar substrates to link source and target. Transform-MinER searches for potential reaction centers in the source substrate and uses chemoinformatic fingerprints to identify those that are situated in molecular environments similar to native counterparts, prioritizing steps that move closer to the target using reactions most similar to native in its exploration of search space. The ligand-based methodology behind Transform-MinER is presented, and its performance is validated yielding 90% success rates: first, on a data set of native pathways from the KEGG database, and second, on a data set of de novo enzyme reactions.
['Tyzack|Jonathan D|JD|0000-0003-4827-9023', 'Ribeiro|Antonio J M|AJM|', 'Borkakoti|Neera|N|', 'Thornton|Janet M|JM|']
D000446:Aldehyde-Lyases D000465:Algorithms D055162:Biocatalysis D000080911:Cheminformatics D057225:Data Mining D062126:Databases, Chemical D008024:Ligands D000068900:Sitagliptin Phosphate D012984:Software D013379:Substrate Specificity D058615:Synthetic Biology D013678:Technology, Pharmaceutical D000637:Transaminases
enzyme design chemoinformatics data-mining molecular fingerprints promiscuity synthetic biology