A Coculture Based Tyrosine-Tyrosinase Electrochemical Gene Circuit for Connecting Cellular Communication with Electronic Networks

VanArsdale, Eric; Hörnström, David; Sjöberg, Gustav; Järbur, Ida; Pitzer, Juliana; Payne, G. L.; Maris, Antonius J. A. van; Bentley, William E.

doi:10.1021/acssynbio.9b00469

Cited by 24 publications

(26 citation statements)

References 81 publications

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“…[ 31,75–77 ] Finally, we suggest that catechols could emerge as important molecular circuit elements for miniaturize‐able, deployable and sustainable systems for redox‐linked bioelectronics. [ 78–84 ]…”

Section: Discussionmentioning

confidence: 99%

Hydrogel Patterning with Catechol Enables Networked Electron Flow

Zhao

Rzasa

et al. 2021

Adv Funct Materials

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Reduction–oxidation (redox) reactions provide a distinct modality for biological communication that is fundamentally different from the more‐familiar ion‐based electrical modality. Biology uses these two modalities for communication through different systems (immune versus nervous), and uses different mechanisms to control the flow of the charge carriers: the flow of soluble ions is controlled using structural barriers (i.e., membranes) and gates (e.g., membrane‐spanning protein channels), while the flow of insoluble electrons is controlled using redox‐reaction networks. Here, a simple electrochemical approach to pattern catechols onto a flexible polysaccharide hydrogel is reported and it is demonstrated that the patterned catechol regions serve as nodes for the mediated flow of electrons through redox reactions. Electron flow through this node involves the switching of binary redox states (oxidized and reduced) and this node's redox state can be detected (i.e., “read”) by passively observing its optical absorbance, or actively switching its redox‐state electrochemically. Further, this catechol node can be switched through biological mechanisms, and this enables the fabricated catechol node to be embedded within biochemical redox reaction networks to facilitate the spanning of bio‐electronic communication. Thus, it is envisioned that catechols can emerge as a molecular equivalent to a transistor for miniaturize‐able, deployable and sustainable redox‐linked bioelectronics.

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Section: Discussionmentioning

confidence: 99%

Hydrogel Patterning with Catechol Enables Networked Electron Flow

Zhao

Rzasa

et al. 2021

Adv Funct Materials

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“…The agarose thickness varied between 1-3 mm, yielding a diffusional timescale between 1-8 min that agrees with our fastest response times. Thus, our living electronic sensor specifically detects analytes at environmentally-relevant concentrations and conditions with mass-transfer limited kinetics that are up to 10 times faster than the previous state-of-the-art ( 8 – 12 , 27 – 29 , 31 ).…”

Section: Main Textmentioning

confidence: 99%

“…This work describes three parallel innovations beyond previous work ( 27 – 29 , 31 ) required to achieve real-time sensing. First, our work introduces synthetic signal transduction using ET, in addition to phosphorylation ( 32 ) or proteolysis ( 33 ).…”

Section: Main Textmentioning

confidence: 99%

Real-time environmental monitoring of contaminants using living electronic sensors

Atkinson

Zhang

et al. 2021

Preprint

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Real-time chemical sensing is needed to counter the global threats posed by pollution. We combine synthetic biology and materials engineering to develop a living bioelectronic sensor platform with minute detection times. Escherichia coli was programmed to reduce an electrode in a chemical-dependent manner using a modular, eight-component, synthetic electron transport chain. This strain produced significantly more current upon exposure to thiosulfate, an anion that causes microbial blooms. Incorporating a protein switch into the synthetic pathway and encapsulation of microbes with electrodes and conductive nanomaterials yielded a living bioelectronic sensor that could detect an endocrine disruptor within two minutes in riverine water, implicating the signal as mass transfer limited. These findings provide a new platform for miniature, low-power sensors that safeguard ecological and human health.

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“…Tyrosinase is the rate‐limiting enzyme for the first step of melanin biosynthesis, 3,4 catalyzing the hydroxylation of l ‐tyrosine to 3,4‐dihydroxyphenylalanine ( l ‐DOPA) and its further oxidation to dopaquinone 5 . Then, dopaquinone is converted to melanin in a multi‐step process involving enzymes tyrosinase related protein 1 (TYRP1) and dopachrome tautomerase (DCT/TYRP2).…”

Section: Introductionmentioning

confidence: 99%

Thioxothiazolidin derivative, 4‐OST, inhibits melanogenesis by enhancing the specific recruitment of tyrosinase‐containing vesicles to lysosome

Isogawa

Asano

Hayazaki

et al. 2021

J of Cellular Biochemistry

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Tyrosinase catalyzes the rate‐limiting step in melanin synthesis. Melanin is synthesized from l‐tyrosin in the melanosomes, where tyrosinase and other melanogenic factors are recruited via the vesicle transport system. Genetic and biochemical approaches have revealed a correlation between impairments in the vesicle transport system and albinism. However, the specificity of the individual transport systems for the corresponding melanogenic factors has not been well elucidated yet. Here, we report that the thioxothiazolidin derivative, 4‐OST (4‐[(5E)‐5‐[(4‐fluorophenyl)methylidene]‐4‐oxo‐2‐sulfanylidene‐1,3‐thiazolidin‐3‐yl]‐4‐azatricyclo [5.2.1.02,6]dec‐8‐ene‐3,5‐dione: CAS RN. 477766‐87‐3) strongly inhibited melanogenesis in mouse melanoma B16F10 cells. 4‐OST reduces tyrosinase protein levels without affecting its messenger RNA levels or enzymatic activity. Although a reduction in tyrosinase protein level was observed in the presence of a protein synthesis inhibitor, the reduction may be coupled with protein synthesis. Similarly, GIF‐2202 (a derivative of 4‐OST) lowers tyrosinase protein levels without affecting the levels of another melanogenic enzyme, tyrosinase‐related protein 1 (TYRP1) level. The reduction in tyrosinase protein level is associated with an increase in the levels of the lysosomal proteinase cathepsin S. Chloroquine, a lysosome inhibitor, restored the tyrosinase protein level downregulated by GIF‐2202, although no effects of other inhibitors (against proteasome, autophagy, or exocytosis) were observed. In addition, GIF‐2202 segregated the immunofluorescence signals of tyrosinase from those of TYRP1. Chloroquine treatment resulted in co‐localization of tyrosinase and cathepsin S signals near the perinuclear region, suggesting that 4‐OST and GIF‐2202 may alter the destination of the tyrosinase vesicle from the melanosome to the lysosome. 4‐OST and GIF‐2202 can be new tools for studying the tyrosinase‐specific vesicle transport system.

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A Coculture Based Tyrosine-Tyrosinase Electrochemical Gene Circuit for Connecting Cellular Communication with Electronic Networks

Cited by 24 publications

References 81 publications

Hydrogel Patterning with Catechol Enables Networked Electron Flow

Hydrogel Patterning with Catechol Enables Networked Electron Flow

Real-time environmental monitoring of contaminants using living electronic sensors

Thioxothiazolidin derivative, 4‐OST, inhibits melanogenesis by enhancing the specific recruitment of tyrosinase‐containing vesicles to lysosome

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