Allosteric transcription factors as peptide sensors

Modular intracellular peptide sensors for programmable gene control

Background

Synthetic biology increasingly relies on precise gene regulation systems that can sense and respond to specific molecular signals inside living cells. Peptides and peptide-tagged proteins are especially important targets because they govern communication, signaling, and metabolic pathways, yet current sensing systems are constrained by inefficient natural quorum sensing mechanisms. These pathways require peptides to be exported, processed extracellularly, and re-imported before activating transcription, making them difficult to engineer and unreliable across hosts or cell-free systems. Most existing platforms also lack modularity, struggle to detect modified peptides, and cannot easily multiplex orthogonal circuits, limiting the construction of advanced programmable networks for therapeutics, diagnostics, or industrial biomanufacturing. The need for direct, tunable, and context-independent peptide sensing tools has grown as researchers seek to build more sophisticated and customizable biological systems.

Technology Overview

This technology introduces a programmable gene regulation platform based on peptide-sensing allosteric transcription factors, that function through direct intracellular peptide binding. Engineered peptides, which can incorporate amino acid substitutions, terminal modifications, non-natural amino acids, or fusion to other proteins, activate their cognate transcription factor inside the cell to modulate target gene expression without requiring secretion or extracellular processing. The platform supports highly orthogonal sensing through multiple engineered transcription factor and peptide pairs, enabling multiplexed regulatory circuits in both prokaryotic and eukaryotic hosts as well as cell-free systems. The system’s modular design allows customization of sensing specificity and programmable control over gene expression, and its ability to detect peptide-tagged proteins provides a powerful tool for real-time monitoring and dynamic control of cellular processes. Experimental validation demonstrates quantitative, tunable responses and robust performance across diverse biological environments.

Benefits

Direct intracellular peptide sensing without export or processing
Highly modular design enables customizable specificity and tuning
Supports multiplexed, orthogonal regulatory circuits
Compatible with prokaryotic, eukaryotic, and cell-free systems
Detects peptide-tagged proteins for real-time process monitoring

Commercial Applications

Synthetic biology circuit design
Programmable therapeutics
Biosensing and diagnostics
Metabolic engineering
Cell-free biomanufacturing

Opportunity

Provides a versatile, engineerable platform for advanced gene regulation
Enables development of next-generation biosensors, programmable therapies, and multiplexed synthetic circuits
Broad applicability across research, biomanufacturing, and diagnostic markets
Available for exclusive licensing