Biological nanopore control of synthesis: Single-molecule reaction and characterization

In contemporary biopolymer synthesis, conservative synthesis of monomers to polymers has been achieved by using organocatalyst. However, the high-efficiency conversion in biopolymer synthesis is rare, due to the difficulties in precisely monitoring and controlling the reaction immediates1,2. Here, we report a novel molecular machine for controllable single-biomolecule synthesis with biological protein nanopore (NP-Synth.), which combines the advantages of manipulating reaction sites at atomically level and real-time recording of the reaction trajectories. Driven by the applied voltage, the two reactant molecules from the reducing phase successively enters into the nanopore confinement. The catalytical site inside the nanopore facilitates the rapid conjugation of these two molecules. The nanopore confinement here directs the orientation of the reactive group of the reactant for directly driving the synthesis. Following the real-time current traces, the reaction process is optimized by adjusting the length of the reactant and the applied potential. This work shows that the NP-Synth. can produce, by combining well-defined protein nanopore, ordered biopolymers that were previously inaccessible to organic chemistry.