Concatenated logic gates using four coupled biocatalysts operating in series

Abstract

The assembly of three concatenated enzyme-based logic gates consisting of OR, AND, XOR is described. Four biocatalysts, acetylcholine esterase, choline oxidase, microperoxidase-11, and the NAD ؉ -dependent glucose dehydrogenase, are used to assemble the gates. Four inputs that include acetylcholine, butyrylcholine, O2, and glucose are used to drive the concatenated-gates system. The cofactor NAD ؉ , and its reduced 1,4-dihydro form, NADH, are used as a reporter couple, and these provide an optical output for the gates. The modulus of the absorbance changes of NADH is used as a readout signal.biocomputers ͉ biocatalysis ͉ enzymes T he hardware of computers consists of parallel and serial logic-gate operations that are triggered by electronic inputs. These functions may be duplicated by appropriately designed chemical or biological systems. Different molecular and supramolecular assemblies that operate as logic gates and perform molecular-scale arithmetic operations were discussed (1-9). Similarly, biomolecules such as nucleic acids or proteins were used as active components that perform logic-gate operations (10-15). Gene-based artificial circuits acting as bistable toggle switches (16) or oscillators (17) were developed, and coupled enzyme͞DNA systems that perform programmable biochemical transformations that mimic basic computing of finite automaton were reported (17). The use of enzymes as the active components for logic gate functions is specifically intriguing because numerous biocatalytic cycles in nature rely on information processing, revealing similarities to computer devices. Although the function of enzyme networks as mimics of Boolean logic gates was discussed (18), and the potential use of enzymes as building units of high-density computing architectures was addressed (19), the experimental work that validates biocatalyst-stimulated logic gate operations is quite scarce, and lacks the desired complexity that resembles computers. Single enzyme-based logic-gate operations were reported. For example, the dynamic conformational changes of malate dehydrogenase in response to Mg ϩ and Ca 2ϩ ions acting as inputs was used to develop a XOR gate (20). Also, a modified enzyme and its inhibitor were used as inputs that activated an AND gate (21). Recently, we have reported on the assembly of coupled biocatalytic systems that mimic OR, XOR, AND, or InhibAND logic-gate functions (22), and the use of these systems for elementary arithmetic operations (halfadder and half-subtractor) was demonstrated (23). In none of these systems was the consecutive operation of several gates that operate in series demonstrated. This feature is, however, essential to develop any future ''computer-like'' function of enhanced complexity. Here, we report on the assembly of a four-enzymecoupled system that includes four inputs and performs in series three logic-gate operations OR, AND, and XOR. Results and DiscussionsThe system and its operation is depicted in Fig. 1A and consists of the four biocatalysts, acetylcholine esterase (AChE)...

Optimization of Enzymatic Biochemical Logic for Noise Reduction and Scalability: How Many Biocomputing Gates Can Be Interconnected in a Circuit?

“…29,30 Longer-term, however, the problem of "analog" noise reduction in biochemical logic should be considered within a broader context: Our present study has identified the source of the difficulty as follows. Gate optimization involves modification of the gate function, z = F(x,y), which changes the slope of various cross-sections of this function, some of which were marked in Figure 4(B).…”

“…Using the advantages of enzyme-based logic gates, biocomputing "devices" such as a biomolecular half-adder, a half-subtractor 28 and keypad lock 29 were assembled to demonstrate systems with computational functionality composed of several concatenated logic gates. 29,30 1.2. Motivation.…”

Implementation of simple logic gates on gold–ammonia bonding patterns in different charge states

“…[5][6][7][8][9][10] In parallel, several groups have shown that it is possible realize complex combinational logic circuits at the molecular scale, up to half and full addition or subtraction using various external perturbations, i.e., chemical, biochemical, photochemical, optical, electrochemical, electrical, to address the system, encode the inputs and perform the logic operations. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] We propose here another approach for implementing molecular logic gates.…”

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“…For example, Willner, Katz and their colleagues combine acetylcholine esterase, choline oxidase, microperoxidase and glucose dehydrogenase to achieve the minimized gate array shown in Figure 7. 94 The 85 selectivity of acetylcholine esterase is not so extreme. So it hydrolyzes acetylcholine and butyrylcholine with comparable efficiency in an OR logical manner.…”