A small-molecule chemical interface for molecular programs
| Autor: | Camille Lescanne, Vasily A Shenshin, Guillaume Gines, Yannick Rondelez |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
AcademicSubjects/SCI00010 Interface (computing) Bioengineering 02 engineering and technology DNA-Directed DNA Polymerase Biology 03 medical and health sciences Allosteric Regulation Genetics Tryptophan Synthase Sensitivity (control systems) Layer (object-oriented design) Electronic circuit Fluorescent Dyes Signal processing business.industry DNA Modular design 021001 nanoscience & nanotechnology Small molecule DNA-Binding Proteins 030104 developmental biology Exodeoxyribonucleases Pattern recognition (psychology) 0210 nano-technology Biological system business Synthetic Biology and Bioengineering |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | In vitro molecular circuits, based on DNA-programmable chemistries, can perform an increasing range of high-level functions, such as molecular level computation, image or chemical pattern recognition and pattern generation. Most reported demonstrations, however, can only accept nucleic acids as input signals. Real-world applications of these programmable chemistries critically depend on strategies to interface them with a variety of non-DNA inputs, in particular small biologically relevant chemicals. We introduce here a general strategy to interface DNA-based circuits with non-DNA signals, based on input-translating modules. These translating modules contain a DNA response part and an allosteric protein sensing part, and use a simple design that renders them fully tunable and modular. They can be repurposed to either transmit or invert the response associated with the presence of a given input. By combining these translating-modules with robust and leak-free amplification motifs, we build sensing circuits that provide a fluorescent quantitative time-response to the concentration of their small-molecule input, with good specificity and sensitivity. The programmability of the DNA layer can be leveraged to perform DNA based signal processing operations, which we demonstrate here with logical inversion, signal modulation and a classification task on two inputs. The DNA circuits are also compatible with standard biochemical conditions, and we show the one-pot detection of an enzyme through its native metabolic activity. We anticipate that this sensitive small-molecule-to-DNA conversion strategy will play a critical role in the future applications of molecular-level circuitry. |
| Databáze: | OpenAIRE |
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