Quantum-inspired logic for advanced Transcriptional Programming

The tenets of intelligent biological systems are (i) scalable decision-making, (ii) inheritable memory, and (iii) communication. This study aims to increase the complexity of decision-making operations beyond standard Boolean logic, while minimizing the metabolic burden imposed on the chassis cell. To this end, we present a new platform technology for constructing genetic circuits with multiple OUTPUT gene control using fewer INPUTs relative to conventional genetic circuits. Inspired by principles from quantum computing, we engineered synthetic bidirectional promoters, regulated by synthetic transcription factors, to construct 1-INPUT, 2-OUTPUT logical operations-i.e. biological QUBIT and PAULI-X logic gates-designed as compressed genetic circuits. We then layered said gates to engineer additional quantum-inspired logical operations of increasing complexity-e.g. FEYNMAN and TOFFOLI gates. In addition, we engineered a 2-INPUT, 4-OUTPUT quantum operation to showcase the capacity to utilize the entire permutation INPUT space. Finally, we developed a recombinase-based memory operation to remap the truth table between two disparate logic gates-i.e. converting a QUBIT operation to an antithetical PAULI-X operation in situ. This study introduces a novel and versatile synthetic biology toolkit, which expands the biocomputing capacity of Transcriptional Programming via the development of compressed and scalable multi-INPUT/OUTPUT logical operations.