Synthetic Biological Circuits within an Orthogonal Central Dogma.

Synthetic biology strives to reliably control cellular behavior, typically in the form of user-designed interactions of biological components to produce a predetermined output. Engineered circuit components are frequently derived from natural sources and are therefore often hampered by inadvertent interactions with host machinery, most notably within the host central dogma. Reliable and predictable gene circuits require the targeted reduction or elimination of these undesirable interactions to mitigate negative consequences on host fitness and develop context-independent bioactivities. Here, we review recent advances in biological orthogonalization, namely the insulation of researcher-dictated bioactivities from host processes, with a focus on systematic developments that may culminate in the creation of an orthogonal central dogma and novel cellular functions.

• Publication year

  2020

• Venue

  Trends in Biotechnology

• Publication date

  2020-06-22

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.1016/j.tibtech.2020.05.013PMID 32586633PMCID PMC7746572
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Rapid discovery and evolution of orthogonal aminoacyl-tRNA synthetase–tRNA pairs

  2020cited by this paper
• New codons for efficient production of unnatural proteins in a semi-synthetic organism

  2020cited by this paper
• De novo design of protein logic gates

  2020cited by this paper
• Bacterial RNA Degradosomes: Molecular Machines under Tight Control.

  2020cited by this paper
• Automated continuous evolution of proteins in vivo

  2020cited by this paper
• Engineering Epigenetic Regulation Using Synthetic Read-Write Modules.

  2019cited by this paper
• De-Novo-Designed Translation-Repressing Riboregulators for Multi-Input Cellular Logic

  2019cited by this paper
• Strategies for in vitro engineering of the translation machinery

  2019cited by this paper
• Genetic Compatibility and Extensibility of Orthogonal Replication.

  2019cited by this paper
• Optimization of Replication, Transcription, and Translation in a Semi-Synthetic Organism.

  2019cited by this paper
• Hachimoji DNA and RNA: A genetic system with eight building blocks

  2019cited by this paper
• Engineered ribosomes with tethered subunits for expanding biological function

  2019cited by this paper
• Gene networks that compensate for crosstalk with crosstalk

  2019cited by this paper
• A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids

  2019cited by this paper
• Modular Analysis and Design of Biological Circuits.

  2019cited by this paper
• Reading, writing and erasing mRNA methylation

  2019cited by this paper
• Total synthesis of Escherichia coli with a recoded genome

  2019cited by this paper
• Mutually Orthogonal Nonsense-Suppression Systems and Conjugation Chemistries for Precise Protein Labeling at up to Three Distinct Sites.

  2019cited by this paper
• Escherichia coli “Marionette” strains with 12 highly optimized small-molecule sensors

  2018influential reference
• Versatility of Synthetic tRNAs in Genetic Code Expansion

  2018cited by this paper
• Scalable continuous evolution of genes at mutation rates above genomic error thresholds

  2018cited by this paper
• Mutually Orthogonal DNA Replication Systems In Vivo.

  2018cited by this paper
• Toward an orthogonal central dogma.

  2018cited by this paper
• Mutually orthogonal pyrrolysyl-tRNA synthetase/tRNA pairs

  2018cited by this paper
• A sigma factor toolbox for orthogonal gene expression in Escherichia coli

  2018cited by this paper
• A multi-landing pad DNA integration platform for mammalian cell engineering

  2018cited by this paper
• Self-replication of DNA by its encoded proteins in liposome-based synthetic cells

  2018cited by this paper
• A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into Bacteria.

  2018cited by this paper
• Self-replication of circular DNA by a self-encoded DNA polymerase through rolling-circle replication and recombination

  2018cited by this paper
• De novo Design of Translational RNA Repressors

  2018cited by this paper
• Controlling orthogonal ribosome subunit interactions enables evolution of new function

  2018cited by this paper
• CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes.

  2017cited by this paper
• Burden-driven feedback control of gene expression

  2017cited by this paper
• Continuous directed evolution of aminoacyl-tRNA synthetases

  2017cited by this paper
• Cell-free and in vivo characterization of Lux, Las, and Rpa quorum activation systems in E. coli

  2017cited by this paper
• A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information

  2017cited by this paper
• Rewriting the Genetic Code.

  2017cited by this paper
• Resource Competition Shapes the Response of Genetic Circuits

  2017cited by this paper
• Overloaded and stressed: whole-cell considerations for bacterial synthetic biology.

  2016cited by this paper
• DNAmod: the DNA modification database

  2016cited by this paper
• Post-transcriptional gene regulation by mRNA modifications

  2016cited by this paper
• A CRISPR-based approach for targeted DNA demethylation

  2016cited by this paper
• Measurements of translation initiation from all 64 codons in E. coli

  2016cited by this paper
• In Vivo Biosynthesis of a β-Amino Acid-Containing Protein.

  2016cited by this paper
• Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses.

  2016cited by this paper
• Genetic circuit design automation

  2016cited by this paper
• Complex transcriptional modulation with orthogonal and inducible dCas9 regulators

  2016cited by this paper
• DNA-Binding Proteins Essential for Protein-Primed Bacteriophage Φ29 DNA Replication

  2016cited by this paper
• Ribosome Subunit Stapling for Orthogonal Translation in E.  coli

  2015cited by this paper
• Protein synthesis by ribosomes with tethered subunits

  2015influential reference
• Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids

  2015cited by this paper
• Transcription yield of fully 2′-modified RNA can be increased by the addition of thermostabilizing mutations to T7 RNA polymerase mutants

  2015cited by this paper
• Ribosome Subunit Stapling for Orthogonal Translation in E. coli

  2015cited by this paper
• Isocost Lines Describe the Cellular Economy of Genetic Circuits

  2015cited by this paper
• Epigenome editing by a CRISPR/Cas9-based acetyltransferase activates genes from promoters and enhancers

  2015cited by this paper
• Directed Evolution of a Panel of Orthogonal T7 RNA Polymerase Variants for in Vivo or in Vitro Synthetic Circuitry.

  2015cited by this paper
• Optimized orthogonal translation of unnatural amino acids enables spontaneous protein double-labelling and FRET

  2014cited by this paper
• A brief history of synthetic biology

  2014cited by this paper
• A load driver device for engineering modularity in biological networks

  2014cited by this paper
• Principles of genetic circuit design

  2014cited by this paper
• Modular construction of mammalian gene circuits using TALE transcriptional repressors

  2014cited by this paper
• Bacterial growth: global effects on gene expression, growth feedback and proteome partition.

  2014cited by this paper
• Designing logical codon reassignment – Expanding the chemistry in biology

  2014cited by this paper
• Highly-efficient Cas9-mediated transcriptional programming

  2014cited by this paper
• Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet

  2014cited by this paper
• An orthogonal DNA replication system in yeast.

  2014cited by this paper
• Cell-free Protein Synthesis from a Release Factor 1 Deficient Escherichia coli Activates Efficient and Multiple Site-specific Nonstandard Amino Acid Incorporation

  2013cited by this paper
• Visualization of evolutionary stability dynamics and competitive fitness of Escherichia coli engineered with randomized multigene circuits.

  2013cited by this paper
• CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering

  2013cited by this paper
• Retroactivity controls the temporal dynamics of gene transcription.

  2013cited by this paper
• An expanded genetic code in mammalian cells with a functional quadruplet codon.

  2013cited by this paper
• Genomically Recoded Organisms Expand Biological Functions

  2013cited by this paper
• CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes.

  2013cited by this paper
• Design of orthogonal genetic switches based on a crosstalk map of σs, anti-σs, and promoters

  2013influential reference
• Directed evolution of genetic parts and circuits by compartmentalized partnered replication

  2013cited by this paper
• One core, two shells: bacterial and eukaryotic ribosomes

  2012cited by this paper
• Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma

  2012cited by this paper
• Modular control of multiple pathways using engineered orthogonal T7 polymerases

  2012cited by this paper
• Genetic switchboard for synthetic biology applications

  2012cited by this paper
• Recent advances in genetic code engineering in Escherichia coli.

  2012cited by this paper
• A synthetic biology framework for programming eukaryotic transcription functions.

  2012cited by this paper
• Synthetic Genetic Polymers Capable of Heredity and Evolution

  2012cited by this paper
• Genetic circuit performance under conditions relevant for industrial bioreactors.

  2012cited by this paper
• Contextualizing context for synthetic biology – identifying causes of failure of synthetic biological systems

  2012cited by this paper
• Supplementary information for Rationally designed families of orthogonal RNA regulators of translation

  2012cited by this paper
• DNA phosphorothioation is widespread and quantized in bacterial genomes

  2011cited by this paper
• Amplification, mutation, and sequencing of a six-letter synthetic genetic system.

  2011cited by this paper
• RF1 Knockout Allows Ribosomal Incorporation of Unnatural Amino Acids at Multiple Sites

  2011cited by this paper
• Rapid optimization of gene dosage in E. coli using DIAL strains

  2011cited by this paper
• Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome

  2010influential reference
• Adding new chemistries to the genetic code.

  2010cited by this paper
• The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) σ factor protein family

  2009cited by this paper
• Emergent bistability by a growth-modulating positive feedback circuit.

  2009cited by this paper
• Synthesis of orthogonal transcription-translation networks

  2009cited by this paper
• Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

  2008cited by this paper
• Regulation of bacterial RNA polymerase sigma factor activity: a structural perspective.

  2008cited by this paper
• Modular cell biology: retroactivity and insulation

  2008cited by this paper
• Directed Evolution of AraC for Improved Compatibility of Arabinose- and Lactose-Inducible Promoters

  2007cited by this paper
• Computational systems biology in cancer: modeling methods and applications.

  2007cited by this paper
• Transcription Initiation by Mix and Match Elements: Flexibility for Polymerase Binding to Bacterial Promoters

  2007cited by this paper

• From domination to partnership

  2026cites this paper
• De novo design of synthetic microbial genomes

  2026cites this paper
• Growth control as a central regulator for tuning the cellular context

  2025cites this paper
• Building an expanded bio-based economy through synthetic biology.

  2025cites this paper
• Chronogenetic medicine: principles, engineering, and applications of circadian-based drug delivery systems

  2025cites this paper
• Natural and artificial variations of the standard genetic code.

  2025cites this paper
• Pyruvate-responsive genetic circuit biosensors for remodeling and dynamically controlling central carbon metabolism in the eukaryotic chassis

  2025cites this paper
• Role of intercellular interactions on single cell and population level responses: considerations for multicellular bioreporter design

  2025cites this paper
• Functional analysis of a mesocarp-specific MSP-C7 promoter from oil palm (Elaeis guineensis Jacq.)

  2025cites this paper
• Defining bottlenecks and physiological impact of an orthogonal translation initiation system

  2025cites this paper
• Development and application of a highly specific whole-cell biosensor for supersulfide detection in environmental samples.

  2025cites this paper
• Biosensor characterization: formal methods from the perspective of proteome fractions

  2025cites this paper
• Towards a rational approach to promoter engineering: understanding the complexity of transcription initiation in prokaryotes

  2024cites this paper
• Designed to breathe: synthetic biology applications in plant hypoxia.

  2024cites this paper
• Assembly of functional microbial ecosystems: from molecular circuits to communities

  2024cites this paper
• Recoded gene circuits for multiplexed genetic code expansion

  2024cites this paper
• Fine-Tuning Genetic Circuits via Host Context and RBS Modulation

  2024cites this paper
• Mobius Assembly for Plant Systems highlights promoter-coding sequences-terminator interaction in gene regulation

  2024cites this paper
• Relieving metabolic burden to improve robustness and bioproduction by industrial microorganisms.

  2024cites this paper
• Biosensors Characterization: Formal methods from the Perspective of Proteome Fractions

  2024cites this paper
• Synthetic gene circuit evolution: Insights and opportunities at the mid-scale.

  2024cites this paper
• Chromosomal engineering of inducible isopropanol- butanol-ethanol production in Clostridium acetobutylicum

  2023cites this paper
• Modelling genetic stability in engineered cell populations

  2023cites this paper
• Versatile Strategy for the Construction of a Transcription Factor-Based Orthogonal Gene Expression Toolbox in Monascus spp.

  2023cites this paper
• Advances in plant synthetic biology approaches to control expression of gene circuits.

  2023cites this paper
• Rethinking Biosynthesis of Aclacinomycin A

  2023cites this paper
• GKLOMLI: a link prediction model for inferring miRNA–lncRNA interactions by using Gaussian kernel-based method on network profile and linear optimization algorithm

  2023cites this paper
• Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions

  2023cites this paper
• Plant Promoters and Terminators for High-Precision Bioengineering

  2023cites this paper
• Deploying synthetic coevolution and machine learning to engineer protein-protein interactions

  2023cites this paper
• Illuminating the inner workings of a natural protein switch: Blue-light sensing in LOV-activated diguanylate cyclases

  2023cites this paper
• Microbial cell factory optimisation using genome-wide host-pathway interaction screens

  2023cites this paper
• Synthetic biology encompasses metagenomics, ecosystems, and biodiversity sustainability within its scope

  2023cites this paper
• Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions

  2023cites this paper
• A Genetic Circuit Design for Targeted Viral RNA Degradation

  2023cites this paper
• Developing Synthetic Methylotrophs by Metabolic Engineering-Guided Adaptive Laboratory Evolution.

  2022cites this paper
• Tuning the Transcriptional Activity of the CaMV 35S Promoter in Plants by Single-Nucleotide Changes in the TATA Box

  2022cites this paper
• Shaping bacterial gene expression by physiological and proteome allocation constraints

  2022cites this paper
• SynBio 2.0, a new era for synthetic life: Neglected essential functions for resilience.

  2022cites this paper
• Unlocking the bacterial domain for industrial biotechnology applications using universal parts and tools.

  2022cites this paper
• Feedforward Loops: Evolutionary Conserved Network Motifs Redesigned for Synthetic Biology Applications

  2022cites this paper
• Genetic modification, intercellular communication, and epigenetic regulation in plants: An outlook.

  2022cites this paper
• “Toehold Switches; a foothold for Synthetic Biology”

  2022cites this paper
• Mutant polymerases capable of 2′ fluoro-modified nucleic acid synthesis and amplification with improved accuracy

  2022cites this paper
• Learning transcriptome dynamics for discovery of optimal genetic reporters of novel compounds

  2022cites this paper
• An orthogonal metabolic framework for one-carbon utilization

  2021cites this paper
• Engineering and standardization of posttranscriptional biocircuitry in Saccharomyces cerevisiae.

  2021cites this paper
• Trends in small organic fluorescent scaffolds for detection of oxidoreductase.

  2021cites this paper
• tRNA mimicking structures to control and monitor biological processes

  2021cites this paper
• Directed evolution of colE1 plasmid replication compatibility: a fast tractable tunable model for investigating biological orthogonality

  2021cites this paper
• Experimental tools to reduce the burden of bacterial synthetic biology

  2021cites this paper
• Structural analysis of an iron-assisted carbon monolayer for delivery of 2-thiouracil

  2021cites this paper
• Heterologous Production of Glycine Betaine Using Synechocystis sp. PCC 6803-Based Chassis Lacking Native Compatible Solutes

  2021cites this paper
• Metabolic Engineering for Large‐Scale Environmental Bioremediation

  2021cites this paper
• Standardization of inducer-activated broad host range expression modules: debugging and refactoring an alkane-responsive AlkS/PalkB device

  2020cites this paper
• Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway

  2020cites this paper
• Architectures for Combined Transcriptional and Translational Resource Allocation Controllers.

  2020cites this paper
• Mediating Ribosomal Competition by Splitting Pools

  2020cites this paper