Enzyme‐Based Logic Gates and Networks with Output Signals Analyzed by Various Methods

Katz, Evgeny

doi:10.1002/cphc.201601402

Cited by 45 publications

(25 citation statements)

References 216 publications

(466 reference statements)

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“…The Boolean logic gates realized with enzyme‐catalyzed reactions belong to a novel, but already well developed research area, in the general framework of unconventional computing, more specifically to the areas of molecular and biomolecular computing . The logic gates have been realized in various enzyme‐based systems, including enzymes bound to electrode surfaces, when bioelectrocatalytic currents have been activated/inhibited by various combinations of input signals . The present system based on the PQQ‐GDH‐CaM bound to the electrode surface depends on the presence of two activating substrates, Ca 2+ cations and M13 peptide.…”

Section: Figurementioning

confidence: 99%

Bioelectrocatalytic Electrodes Modified with PQQ‐Glucose Dehydrogenase‐Calmodulin Chimera Switchable by Peptide Signals: Pathway to Generic Bioelectronic Systems Controlled by Biomolecular Inputs

et al. 2019

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Construction of artificial allosteric protein switches is one of the central goals of synthetic biology that holds promise to transform the way we detect and quantify substances in vitro and in vivo. An artificial chimeric fusion protein of pyrroloquinoline quinone‐dependent glucose dehydrogenase with calmodulin (PQQ‐GDH‐CaM) was covalently attached to graphene nanosheets produced electrochemically on a carbon fiber electrode. The chimeric PQQ‐GDH‐CaM represents an artificial allosteric switch activated by association of a calmodulin‐binding peptide with the Ca2+‐bound calmodulin domain. The activity of the immobilized enzyme was switched between active and inactive states by adding/removing the activating peptide. The peptide‐signal switchable features originated from the enzyme 3D‐structural variations induced by the conformational (folding/unfolding) changes in the connected calmodulin unit upon formation/dissociation of its complex with the specific peptide. The peptide‐activated immobilized PQQ‐GDH‐CaM enzyme displayed direct (non‐mediated) electron transfer to the conducting electrode support upon glucose oxidation. On the contrary, in the absence of the peptide, the inactive form of the enzyme demonstrated very low bioelectrocatalytic activity for glucose oxidation. Since the conformational changes of the PQQ‐GDH‐CaM depend on the presence of Ca2+ cations and the calmodulin‐binding peptide, both of them were used as input signals to control the enzyme activity mimicking a Boolean AND logic gate. The switchable behavior of the enzyme‐modified electrode was studied electrochemically and used to assemble a signal‐switchable biofuel cell. The use of the peptide as the signaling messenger enables the design of generalizable bioelectronic systems controlled by native and synthetic biochemical signaling systems.

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Section: Figurementioning

confidence: 99%

Bioelectrocatalytic Electrodes Modified with PQQ‐Glucose Dehydrogenase‐Calmodulin Chimera Switchable by Peptide Signals: Pathway to Generic Bioelectronic Systems Controlled by Biomolecular Inputs

et al. 2019

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“…Molecular logic gates constitute a wide range of molecular switches that respond to diverse input signals according to the rules of Boolean logic. Since the inception of the first molecular AND logic gate (de Silva et al, 1993), a wide range of “digital” optical switches (de Ruiter and van der Boom, 2011; de Silva and Uchiyama, 2011; Magri and Mallia, 2013; Ling et al, 2015; Akkaya et al, 2017; Katz, 2017; Erbas-Cakmak et al, 2018; Pilarczyk et al, 2018) and related pattern-generating devices (Rout et al, 2012, 2013, 2014; Sarkar et al, 2016; Hatai et al, 2017; Lustgarten et al, 2017; Pode et al, 2017) have been developed and used for various applications, including information processing (de Ruiter and van der Boom, 2011; de Silva and Uchiyama, 2011; Ling et al, 2015; Akkaya et al, 2017; Katz, 2017; Erbas-Cakmak et al, 2018; Pilarczyk et al, 2018), user identification (Rout et al, 2013; Lustgarten et al, 2017; Andréasson and Pischel, 2018), cryptography (Sarkar et al, 2016; Lustgarten et al, 2017), and sensing (Ling et al, 2015; Wu et al, 2017; Erbas-Cakmak et al, 2018; Magri, 2018). These input-dependent systems were initially considered as potential alternatives to conventional transistors and circuits (de Silva et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Molecular Logic as a Means to Assess Therapeutic Antidotes

2019

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An emerging direction in the area of molecular logic and computation is developing molecular-scale devices that can operate in complex biological environments, such as within living cells, which are beyond the reach of conventional electronic devices. Herein we demonstrate, at the proof-of-principle level, how concepts applied in the field of molecular logic gates can be used to convert a simple fluorescent switch (YES gate), which lights up in the presence of glutathione s-transferase (GST), into a medicinally relevant INHIBIT gate that responds to both GST and beta-cyclodextrin (β-CD) as input signals. We show that the optical responses generated by this device indicate the ability to use it as an enzyme inhibitor, and more importantly, the ability to use β-CD as an “antidote” that prevents GST inhibition. The relevance of this system to biomedical applications is demonstrated by using the INHIBIT gate and β-CD to regulate the growth of breast cancer cells, highlighting the possibility of applying supramolecular inputs, commonly used to control the fluorescence of molecular logic gates, as antidotes that reverse the toxic effect of chemotherapy agents. We also show that the effect of β-CD can be prevented by introducing 1-adamantanecarboxylic acid (Ad-COOH) as an additional input signal, indicating the potential of obtaining precise, temporal control over enzyme activity and anticancer drug function.

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“…Multifarious molecular logic gates and circuits have been constructed, [ 1–6 ] for the purpose of overcoming limitations of conventional silicon‐based digital devices. Owing to predominant properties of deoxyribonucleic acid (DNA), DNA‐based logic systems have been fabricated from basic logic gates (YES, OR, AND, IHIBIT etc.)…”

Section: Figurementioning

confidence: 99%

Illuminating Diverse Concomitant DNA Logic Gates and Concatenated Circuits with Hairpin DNA‐Templated Silver Nanoclusters as Universal Dual‐Output Generators

Zhou

Fan

et al. 2020

Advanced Materials

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issues which should be taken seriously. Plenty of logic devices with multi-output signals are implemented by the aid of covalently labeled reporters (e.g., dye or redox), which cause time wastage and high cost. [10][11][12][13][14][15][16][17] In order to generate more than one output signal, it is ineluctable to introduce many other types of substances (e.g., different dyes and unstable hydrogen peroxide), [18,19] which increase complexity of a logic platform and are much detrimental to the repeatability and assembly of different logic systems. In addition, sequence redesign is required for construction of different logic gates, which leads to high cost and low efficiency. Hence, to explore a simple and noncovalent logic platform in a cost-effective manner is urgently demanded.Aimed at surmounting these drawbacks, new DNA-based logic systems should be considered. DNA-templated silver nanoclusters (AgNCs) with excellent fluorescence properties have attracted wide research interests in the field of fabrication of logic devices, [20][21][22][23][24] due to remarkable merits, such as low cost, tunable emission wavelength, ease of preparation, and convenience of utilization in DNA reaction circuits, and noncovalent (so called label-free) and distinctive logic systems could be designed. [21,22,25,26] Recently, a concept of "DNA Janus Logic Pair", also named as "Contrary Logic Pair", was proposed, [18,27] in which two contrary logic gates (positive and negative gates) were obtained via the same one-time reaction, resulting in significant improvement of computing efficiency. However, systematic complexity remains as a constraining factor for effective implementation and integration of DNA-based logic systems. In this study, diverse concomitant contrary logic gates (CCLGs), such as INHIBIT (INH)^IMPLICATION (IMP), XOR^XNOR and MAJORITY (MAJ)^MINORITY (MIN) ("^" stands for "concomitant and contrary"), and extended concatenated logic circuits (e.g., 4-input MAJ||MIN-INH||IMP, "||" stands for "parallel") with specific functions (e.g., parity generator (Pg) and checker (Pc)) were constructed, by utilization of one novel type of hairpin DNA-templated AgNCs (H-AgNCs) as the universal dualfluorescence signal transducer, and based on the mechanism of DNA hybridization and toehold-mediated strand displacement (TSD). Each pair of CCLGs was achieved via the same DNA (YES^NOT, OR^NOR, INHIBIT^IMPLICATION, XOR^XNOR, and MAJORITY^MINORITY) and extended concatenated logic circuits are presented and some of them perform specific functions, such as parity generators and checkers. The introduction of H-AgNCs as noncovalent signal reporters avoids tedious and high-cost labeling procedures. Of note, the concomitant feature of CCLGs attributed to the dual-emitter AgNCs conduces to reducing the time and cost to devise multiple logic gates. As compared to previous ones, this design eliminates numerous substances (e.g., organic dyes) and unstable components (hydrogen peroxide), which not only decreases the complexity of logic performs and impr...

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Enzyme‐Based Logic Gates and Networks with Output Signals Analyzed by Various Methods

Cited by 45 publications

References 216 publications

Bioelectrocatalytic Electrodes Modified with PQQ‐Glucose Dehydrogenase‐Calmodulin Chimera Switchable by Peptide Signals: Pathway to Generic Bioelectronic Systems Controlled by Biomolecular Inputs

Bioelectrocatalytic Electrodes Modified with PQQ‐Glucose Dehydrogenase‐Calmodulin Chimera Switchable by Peptide Signals: Pathway to Generic Bioelectronic Systems Controlled by Biomolecular Inputs

Molecular Logic as a Means to Assess Therapeutic Antidotes

Illuminating Diverse Concomitant DNA Logic Gates and Concatenated Circuits with Hairpin DNA‐Templated Silver Nanoclusters as Universal Dual‐Output Generators

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