A Screening Platform to Identify and Tailor Biocompatible Small-Molecule Catalysts

Area of Science:

• Biotechnology
• Synthetic Biology
• Chemical Biology

Background:

• Introducing new functions into organisms typically requires genetic engineering.
• Developing synthetic catalysts for new biological transformations is challenging due to stringent biocompatibility and cellular condition requirements.

Purpose of the Study:

• To create a high-throughput screening platform for discovering and optimizing biocompatible small-molecule catalysts.
• To couple catalyst activity to a measurable cellular output for rapid assessment.

Main Methods:

• A 96-well screening platform was established.
• Synthetic catalyst activity was linked to the production of non-canonical amino acids.
• Non-canonical amino acids were incorporated into Green Fluorescent Protein (GFP) for a fluorescence-based readout.
• Cellular fitness was assessed based on the efficiency of stop codon suppression.

Main Results:

• The platform provides a common fluorescence readout for diverse catalyst/reaction combinations.
• The system effectively assesses catalyst performance and its impact on cellular fitness.
• Applied to transition-metal-catalyzed deprotection reactions, enabling their evaluation and optimization.

Conclusions:

• This screening platform accelerates the discovery and optimization of biocompatible catalysts.
• It facilitates the introduction of novel chemical functionalities into biological systems.
• The approach integrates chemical catalysis with cellular machinery for functional innovation.