We created artificial neural network type architecture with engineered bacteria to perform reversible and irreversible computation. This may work as new computing system for performing complex cellular computation.

Synthetic genetic devices can perform molecular computation in living bacteria, which may sense more than one environmental chemical signal, perform complex signal processing in a human‐designed way, and respond in a logical manner. IMPLY is one of the four fundamental logic functions and unlike others, it is an “IF‐THEN” constraint‐based logic. By adopting physical hierarchy of electronics in the realm of in‐cell systems chemistry, a full‐spectrum transcriptional cascaded synthetic genetic IMPLY gate, which senses and integrates two environmental chemical signals, is designed, fabricated, and optimized in a single Escherichia coli cell. This IMPLY gate is successfully integrated into a 2‐input‐2‐output integrated logic circuit and showed higher signal‐decoding efficiency. Further, we showed simple application of those devices by integrating them with an inherent cellular process, where we controlled the cell morphology and color in a logical manner. To fabricate and optimize the genetic devices, a new process pipeline named NETWORK Brick is developed. This pipeline allows fast parallel kinetic optimization and reduction in the unwanted kinetic influence of one DNA module over another. A mathematical model is developed and it shows that response of the genetic devices are digital‐like and are mathematically predictable. This single‐cell IMPLY gate provides the fundamental constraint‐based logic and completes the in‐cell molecular logic processing toolbox. The work has significance in the smart biosensor, artificial in‐cell molecular computation, synthetic biology, and microbiorobotics.

Background Frame-shifted genes results in non-functional peptides. Because of this complete loss of function, frame-shifted genes have never been used in constructing synthetic gene circuits. Results Here we report that the function of gene circuits is rescued by a frame-shifted gene, which functions by translating from a non-natural start codon. We report a single nucleotide deletion mutation that developed in the λ-repressor cI within a synthetic genetic NOT gate in Escherichia coli during growth and through this mutation, a non-functional synthetic gene circuit became functional. This mutation resulted in a frame-shifted cI, which showed effective functionality among genetic NOT-gates in Escherichia coli with high regulatory ranges (> 300) and Hill coefficient (> 6.5). The cI worked over a large range of relative copy numbers between the frame-shifted gene and its target promoter. These properties make this frame-shifted gene an excellent candidate for building synthetic gene circuits. We hypothesized a new operating mechanism and showed evidence that frame-shifted cI was translated from non-natural start codon. We have engineered and tested a series of NOT gates made from a library of cI genes, each of which starts from a different codon within the first several amino acids of the frame-shifted cI. It is found that one form with start codon ACA, starting from the 3rd codon had similar repression behavior as the whole frame-shifted gene. We demonstrated synthetic genetic NAND and NOR logic-gates with frame-shifted cI. This is the first report of synthetic-gene-circuits made from a frame-shifted gene. Conclusions This study inspires a new view on frame-shifted gene and may serve as a novel way of building and optimizing synthetic-gene-circuits. This work may also have significance in the understanding of non-directed evolution of synthetic genetic circuits. Electronic supplementary material The online version of this article (10.1186/s13036-019-0151-x) contains supplementary material, which is available to authorized users.