Synthetic protein switches: design principles and applications

Stein, Viktor; Alexandrov, Kirill

doi:10.1016/j.tibtech.2014.11.010

Cited by 146 publications

(154 citation statements)

References 101 publications

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“…We categorize the plethora of engineering examples to date (Figure 4) based on whether photoreception involves light-regulated association (Section Associating Photoreceptors and Optogenetic Applications, Table 2 ) or not (Section Non-associating Photoreceptors and Optogenetic Applications, Table 1). It should be noted that the below strategies mostly represent specific manifestations of more general design concepts that have proven successful in the engineering of allosterically regulated, mostly light-inert proteins (Makhlynets et al, 2015; Stein and Alexandrov, 2015). …”

Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

“…However, the successful design of several light-inert receptors by domain insertion (Makhlynets et al, 2015; Stein and Alexandrov, 2015) strongly suggests that the basic concept is viable and suitable for the regulation of diverse effectors. In a related strategy, the As LOV2 domain is connected via its Jα helix to selected effector domains such that their active site is occluded (Wu et al, 2009).…”

Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

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Photoreceptor engineering

Ziegler

MÃ¶glich

2015

Front. Mol. Biosci.

113

148

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Sensory photoreceptors not only control diverse adaptive responses in Nature, but as light-regulated actuators they also provide the foundation for optogenetics, the non-invasive and spatiotemporally precise manipulation of cellular events by light. Novel photoreceptors have been engineered that establish control by light over manifold biological processes previously inaccessible to optogenetic intervention. Recently, photoreceptor engineering has witnessed a rapid development, and light-regulated actuators for the perturbation of a plethora of cellular events are now available. Here, we review fundamental principles of photoreceptors and light-regulated allostery. Photoreceptors dichotomize into associating receptors that alter their oligomeric state as part of light-regulated allostery and non-associating receptors that do not. A survey of engineered photoreceptors pinpoints light-regulated association reactions and order-disorder transitions as particularly powerful and versatile design principles. Photochromic photoreceptors that are bidirectionally toggled by two light colors augur enhanced spatiotemporal resolution and use as photoactivatable fluorophores. By identifying desirable traits in engineered photoreceptors, we provide pointers for the design of future, light-regulated actuators.

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Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

Photoreceptor engineering

Ziegler

MÃ¶glich

2015

Front. Mol. Biosci.

113

148

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“…Protein-based sensors (TCS, MRTF, FRET, etc.) feature much more chemical diversity due to more functional groups in proteins and the vast number of protein folds (Stein and Alexandrov, 2015). These properties ultimately offer a higher potential to protein-based biosensors in their diversity, sensitivity, and specificity in metabolite-binding capabilities.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Applications and advances of metabolite biosensors for metabolic engineering

Liu

Evans

Zhang

2015

Metabolic Engineering

168

138

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Quantification and regulation of pathway metabolites is crucial for optimization of microbial production bioprocesses. Genetically encoded biosensors provide the means to couple metabolite sensing to several outputs invaluable for metabolic engineering. These include semi-quantification of metabolite concentrations to screen or select strains with desirable metabolite characteristics, and construction of dynamic metabolite-regulated pathways to enhance production. Taking inspiration from naturally occurring systems, biosensor functions are based on highly diverse mechanisms including metabolite responsive transcription factors, two component systems, cellular stress responses, regulatory RNAs, and protein activities. We review recent developments in biosensors in each of these mechanistic classes, with considerations towards how these sensors are engineered, how new sensing mechanisms have led to improved function, and the advantages and disadvantages of each of these sensing mechanisms in relevant applications. We particularly highlight recent examples directly using biosensors to improve microbial production, and the great potential for biosensors to further inform metabolic engineering practices.

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“…For instance, the examples listed above focus on sensing small molecules. The sensing capability can be further expanded by incorporating additional sensing and actuating functions, such as those based on engineered protein switches [51,52]. Moreover, instead of storing the sensory information by regulating gene expression, the memory recorded in DNA molecules in single cells through stimuli-responsive genome editing can provide relatively more stable memory storage [53,54].…”

Section: Diagnosis: Identification Detection and Drug Responsementioning

confidence: 99%

Quantitative and synthetic biology approaches to combat bacterial pathogens

Bethke

Wang

et al. 2017

Current Opinion in Biomedical Engineering

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Antibiotic resistance is one of the biggest threats to public health. The rapid emergence of resistant bacterial pathogens endangers the efficacy of current antibiotics and has led to increasing mortality and economic burden. This crisis calls for more rapid and accurate diagnosis to detect and identify pathogens, as well as to characterize their response to antibiotics. Building on this foundation, treatment options also need to be improved to use current antibiotics more effectively and develop alternative strategies that complement the use of antibiotics. We here review recent developments in diagnosis and treatment of bacterial pathogens with a focus on quantitative biology and synthetic biology approaches.

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Synthetic protein switches: design principles and applications

Cited by 146 publications

References 101 publications

Photoreceptor engineering

Photoreceptor engineering

Applications and advances of metabolite biosensors for metabolic engineering

Quantitative and synthetic biology approaches to combat bacterial pathogens

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