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Exploring Chemical Biosynthetic Design Space with Transform-MinER.

Jonathan D Tyzack1, Antonio J M Ribeiro1, Neera Borkakoti1

  • 1European Molecular Biology Laboratory , European Bioinformatics Institute (EMBL-EBI) , Wellcome Genome Campus , Hinxton CB10 1SD , United Kingdom.

ACS Synthetic Biology
|October 25, 2019
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Summary

Transform-MinER is a web tool for exploring enzyme reactions and chemical space. It aids enzyme design and directed evolution by identifying promising molecular starting points with 90% success.

Keywords:
chemoinformaticsdata-miningenzyme designmolecular fingerprintspromiscuitysynthetic biology

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Area of Science:

  • Biochemistry
  • Computational Chemistry
  • Synthetic Biology

Background:

  • Exploring chemical biosynthetic space is crucial for enzyme design.
  • Directed evolution experiments require efficient methods to identify novel enzymatic pathways.
  • Current tools may lack comprehensive approaches for navigating complex molecular transformations.

Purpose of the Study:

  • To introduce Transform-MinER, a web application for exploring chemical biosynthetic space.
  • To guide users toward optimal starting points for enzyme design and directed evolution.
  • To present a novel ligand-based methodology for enzyme reaction prediction.

Main Methods:

  • Transform-MinER employs two search functionalities: Molecule Search and Path Search.
  • Chemoinformatic fingerprints are utilized to identify reaction centers in substrates.
  • The methodology prioritizes reactions that move closer to a target molecule using native-like transformations.

Main Results:

  • Transform-MinER achieved a 90% success rate in identifying valid enzyme reactions.
  • Performance was validated using native pathways from the KEGG database.
  • The tool demonstrated effectiveness on a dataset of *de novo* enzyme reactions.

Conclusions:

  • Transform-MinER provides a powerful platform for exploring enzymatic transformations.
  • The application effectively aids in enzyme design and directed evolution strategies.
  • The validated 90% success rate highlights the robustness of the underlying methodology.