A Programmable Biomolecular Computing Machine with Bacterial Phenotype Output

Abstract

The main advantage of autonomous biomolecular computing devices over electronic computers is their ability to interact directly with biological systems. No interface is required since all components of molecular computers, including hardware, software, input, and output are molecules that interact in solution along a cascade of programmable chemical events. Here, we demonstrate for the first time that the output of a computation preduced by a molecular finite automaton can be a visible bacterial phenotype. Our 2-symbol-2-state finite automaton utilized linear double-stranded DNA inputs that were prepared by inserting a string of six base pair symbols into the lacZ gene on the pUC18 plasmid. The computation resulted in a circular plasmid that differed from the original pUC18 by either a 9 base pair (accepting state) or 11 base pair insert (unaccepting state) within the lacZ alpha region gene. Upon transformation and expression of the resultant plasmids in E. coli, the accepting state was represented by production of functional beta-galactosidase and formation of blue colonies on X-gal medium. In contrast, the unaccepting state was represented by white colonies due to a shift in the open reading frame of lacZ.

Biomolecular Finite Automata

“…Arrows pointing up and down represent high and low concentration, respectively. produced by a molecular finite automaton, could be a visible bacterial phenotype [44]. As was the case with the above-mentioned finite automata (Figures 9.6 and 9.12), the new system also processed linear dsDNA inputs, transforming them into linear output molecules.…”

“…In 2011, a new molecular cryptosystem for images [43] based on two-symbol two-state finite automata [22,35,44,45] was demonstrated. The automata representing the software were programmed by the choice of several molecules from a library of eight TMs, representing eight transition rules.…”

“…Insertion of these plasmids into living onion cells resulted in either green fluorescent or cyan fluorescent cells as phenotypical output signals. The mathematical model, as well as its implementation using DNA molecules, was based on previously reported finite automata [22,35,44]. Two enzymes, endonuclease and a DNA ligase, as well as ATP, represented the hardware, whereas the automaton software was programmed by the choice of several molecules from a library of eight TMs, representing eight transition rules.…”

“…Unlike the input consuming automata [22,35,43,44], which can only read the input, the transducer is a more advanced and powerful machine because it can read and write information. Explicitly, it gradually transforms the input tape into an output.…”

Peptide‐Based Computation: Switches, Gates, and Simple Arithmetic

“…The response of these systems to additional chemical triggers, as well as to electrochemical and light triggers, has been demonstrated quite frequently [3][4][5][6][7]. Interestingly, many of the recently described logic operations, and also the more complex arithmetic units, were designed based on pursuing dynamic processes instead of simple binding to one operating molecule [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Beyond the basic demonstrations, scientists were able to exploit their new gates as smart devices that control various applications such as catalysis, sensing analytes, drug delivery, and even in vivo transcription.…”