Optogenetics and biosensors set the stage for metabolic cybergenetics.

Cybergenetic systems use computer interfaces to enable feed-back controls over biological processes in real time. The complex and dynamic nature of cellular metabolism makes cybergenetics attractive for controlling engineered metabolic pathways in microbial fermentations. Cybergenetics would not only create new avenues of research into cellular metabolism, it would also enable unprecedented strategies for pathway optimization and bioreactor operation and automation. Implementation of metabolic cybergenetics, however, will require new capabilities from actuators, biosensors, and control algorithms. The recent application of optogenetics in metabolic engineering, the expanding role of genetically encoded biosensors in strain development, and continued progress in control algorithms for biological processes suggest that this technology will become available in the not so distant future.

• Publication year

  2020

• Venue

  Current Opinion in Biotechnology

• Publication date

  2020-09-11

• Fields of study

  Biology, Medicine, Computer Science, Engineering

• Identifiers
  DOI 10.1016/j.copbio.2020.07.012PMID 32932048
• 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.

• Optogenetic control of the lac operon for bacterial chemical and protein production

  2020cited by this paper
• RNA-based fluorescent biosensors for live cell imaging of small molecules and RNAs.

  2020cited by this paper
• Programming Escherichia coli to function as a digital display

  2020cited by this paper
• Genetically encoded biosensors for branched-chain amino acid metabolism to monitor mitochondrial and cytosolic production of isobutanol and isopentanol in yeast

  2020cited by this paper
• Lights up on organelles: Optogenetic tools to control subcellular structure and organization

  2020cited by this paper
• Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold

  2020cited by this paper
• Transcription factor-based biosensors and inducible systems in non-model bacteria: current progress and future directions.

  2020cited by this paper
• Optogenetic control of mRNA localization and translation in live cells

  2020cited by this paper
• Light‐inducible flux control of triosephosphate isomerase on glycolysis in Escherichia coli

  2019cited by this paper
• Optogenetic control of protein binding using light-switchable nanobodies

  2019cited by this paper
• Partial Observations and Conservation Laws: Gray-Box Modeling in Biotechnology and Optogenetics

  2019cited by this paper
• Genetically Encoded Ratiometric RNA-based Sensors for Quantitative Imaging of Small Molecules in Living Cells.

  2019cited by this paper
• A Fluorogenic RNA-Based Sensor Activated by Metabolite-Induced RNA Dimerization.

  2019cited by this paper
• Conversion of Cytochrome P450 2D6 of Human Into a FRET-Based Tool for Real-Time Monitoring of Ajmalicine in Living Cells

  2019cited by this paper
• De Novo Design of Bioactive Protein Switches

  2019cited by this paper
• Next-level riboswitch development—implementation of Capture-SELEX facilitates identification of a new synthetic riboswitch

  2019cited by this paper
• A bright future: optogenetics to dissect the spatiotemporal control of cell behavior.

  2019cited by this paper
• A Regulatory NADH/NAD+ Redox Biosensor for Bacteria.

  2019cited by this paper
• Advances in optogenetic regulation of gene expression in mammalian cells using cryptochrome 2 (CRY2).

  2019cited by this paper
• Two decades of genetically encoded biosensors based on Förster resonance energy transfer.

  2019cited by this paper
• Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives

  2019cited by this paper
• Custom-made transcriptional biosensors for metabolic engineering.

  2019cited by this paper
• Principles and applications of optogenetics in developmental biology

  2019cited by this paper
• Evolution-guided engineering of small-molecule biosensors

  2019cited by this paper
• A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC

  2019cited by this paper
• Light-based control of metabolic flux through assembly of synthetic organelles

  2019cited by this paper
• Optogenetic switch for controlling the central metabolic flux of Escherichia coli.

  2019cited by this paper
• A universal biomolecular integral feedback controller for robust perfect adaptation

  2019cited by this paper
• High-throughput multicolor optogenetics in microwell plates

  2019cited by this paper
• Modular and tunable biological feedback control using a de novo protein switch

  2019cited by this paper
• A blue light receptor that mediates RNA binding and translational regulation

  2019cited by this paper
• A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP

  2018cited by this paper
• A novel optogenetically tunable frequency modulating oscillator

  2018cited by this paper
• Protein phase separation provides long-term memory of transient spatial stimuli

  2018cited by this paper
• Synthetic control systems for high performance gene expression in mammalian cells

  2018cited by this paper
• Programmable protein circuits in living cells

  2018cited by this paper
• Self-Amplifying Pulsatile Protein Dynamics without Positive Feedback.

  2018cited by this paper
• Regulation of Gene Expression and Signaling Pathway Activity in Mammalian Cells by Automated Microfluidics Feedback Control.

  2018cited by this paper
• Bringing Light to Transcription: The Optogenetics Repertoire

  2018cited by this paper
• Optogenetic regulation of transcription

  2018cited by this paper
• Next generation industrial biotechnology based on extremophilic bacteria.

  2018cited by this paper
• Near-infrared light–controlled systems for gene transcription regulation, protein targeting and spectral multiplexing

  2018cited by this paper
• Optogenetic regulation of engineered cellular metabolism for microbial chemical production

  2018cited by this paper
• Current and future modalities of dynamic control in metabolic engineering.

  2018cited by this paper
• A Miniaturized Escherichia coli Green Light Sensor with High Dynamic Range

  2018cited by this paper
• An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation

  2018cited by this paper
• Dynamic control of endogenous metabolism with combinatorial logic circuits

  2018cited by this paper
• Real-Time Genetic Compensation Defines the Dynamic Demands of Feedback Control.

  2018cited by this paper
• Engineering a Model Cell for Rational Tuning of GPCR Signaling

  2018cited by this paper
• At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior.

  2017cited by this paper
• An orthogonal and pH-tunable sensor-selector for muconic acid biosynthesis in yeast

  2017cited by this paper
• Balancing a genetic toggle switch by real-time feedback control and periodic forcing

  2017cited by this paper
• Engineering RGB color vision into Escherichia coli.

  2017cited by this paper
• Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets.

  2017cited by this paper
• RNA-aptamers-in-droplets (RAPID) high-throughput screening for secretory phenotypes

  2017cited by this paper
• Shaping bacterial population behavior through computer-interfaced control of individual cells

  2017cited by this paper
• Development of Transcription Factor-Based Designer Macrolide Biosensors for Metabolic Engineering and Synthetic Biology.

  2017cited by this paper
• Biosensors for Metabolic Engineering

  2016cited by this paper
• Biosensor-based engineering of biosynthetic pathways.

  2016cited by this paper
• Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth

  2016cited by this paper
• Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast.

  2016cited by this paper
• In Vivo Real-Time Control of Gene Expression: A Comparative Analysis of Feedback Control Strategies in Yeast.

  2016cited by this paper
• In Vivo Autofluorescence Spectroscopic Study and Evaluation of DNA Damage By Comet Assay in Smokers.

  2015cited by this paper
• Synthetic biosensors for precise gene control and real-time monitoring of metabolites

  2015cited by this paper
• A general strategy to construct small molecule biosensors in eukaryotes

  2015cited by this paper
• In silico control of biomolecular processes.

  2015cited by this paper
• In-Vivo Real-Time Control of Protein Expression from Endogenous and Synthetic Gene Networks

  2014cited by this paper
• An evaluation of genetically encoded FRET-based biosensors for quantitative metabolite analyses in vivo.

  2014cited by this paper
• Real-time optogenetic control of intracellular protein concentration in microbial cell cultures.

  2014cited by this paper
• Ultraviolet-B-mediated induction of protein–protein interactions in mammalian cells

  2013cited by this paper
• Multi-chromatic control of mammalian gene expression and signaling

  2013cited by this paper
• Long-term model predictive control of gene expression at the population and single-cell levels

  2012cited by this paper
• Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids

  2012cited by this paper
• Light-based feedback for controlling intracellular signaling dynamics

  2011cited by this paper
• In silico feedback for in vivo regulation of a gene expression circuit

  2011cited by this paper
• Multichromatic control of gene expression in Escherichia coli.

  2011cited by this paper
• Cultivation, photobioreactor design and harvesting of microalgae for biodiesel production: a critical review.

  2011cited by this paper
• GS Activation Is Time-limiting in Initiating Receptor-mediated Signaling*

  2006cited by this paper
• FRET imaging

  2003cited by this paper

• Balancing Doses of EL222 and Light Improves Optogenetic Induction of Protein Production in Komagataella phaffii

  2025cites this paper
• A stationary phase-specific bacterial green light sensor for enhancing metabolite production

  2025cites this paper
• Optogenetic tools for optimizing key signalling nodes in synthetic biology.

  2025cites this paper
• The role of metabolic reprogramming in inflammatory bone diseases.

  2025cites this paper
• Capitalizing on mechanistic insights to power design of future-ready intracellular optogenetics tools.

  2025cites this paper
• Lighting up yeast: overview of optogenetics in yeast and their applications to yeast biotechnology

  2025cites this paper
• Leveraging artificial intelligence for efficient microbial production.

  2025cites this paper
• Engineering chimeric signaling proteins for microbial whole-cell biosensors: from design to deployment.

  2025cites this paper
• Lactic Acid Bacteria as Biofactories: Mechanistic Insights, Engineering Strategies, and Future Horizons for Heterologous Enzyme Expression.

  2025cites this paper
• Orthogonal replication with optogenetic selection evolves yeast JEN1 into a mevalonate transporter

  2025cites this paper
• Biotechnology systems engineering: preparing the next generation of bioengineers

  2025cites this paper
• Directing microbial co-culture composition using cybernetic control

  2025cites this paper
• Experimentally implemented dynamic optogenetic optimization of ATPase expression using knowledge-based and Gaussian-process-supported models

  2024cites this paper
• A hybrid in silico/in-cell controller that handles process-model mismatches using intracellular biosensing

  2024cites this paper
• Closed-loop control of active nematic flows

  2024cites this paper
• Cybernetic control of a natural microbial co-culture

  2024cites this paper
• Controlling neural activity: LPV modelling of optogenetically actuated Wilson–Cowan model

  2024cites this paper
• OptMSP: A Toolbox for Designing Optimal Multi-Stage (Bio)Processes.

  2024cites this paper
• Synthetic microbiology in sustainability applications

  2024cites this paper
• Giving the cells what they need when they need it: Biosensor‐based feeding control

  2024cites this paper
• Hybrid physics-informed metabolic cybergenetics: process rates augmented with machine-learning surrogates informed by flux balance analysis

  2024cites this paper
• Monitoring intracellular metabolite concentrations by moving horizon estimation based on kinetic modeling

  2023cites this paper
• High-throughput feedback-enabled optogenetic stimulation and spectroscopy in microwell plates

  2023cites this paper
• Genetically encoded biosensors for microbial synthetic biology: From conceptual frameworks to practical applications.

  2023cites this paper
• Optimal control of bioproduction in the presence of population heterogeneity

  2023cites this paper
• Towards a modeling, optimization and predictive control framework for fed-batch metabolic cybergenetics

  2023cites this paper
• Advances in the dynamic control of metabolic pathways in Saccharomyces cerevisiae

  2023cites this paper
• Diya – A universal light illumination platform for multiwell plate cultures

  2023cites this paper
• Emerging optogenetics technologies in biomedical applications

  2023cites this paper
• Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics

  2023cites this paper
• Batch-to-Batch Optimization with Model Adaptation Leveraging Gaussian Processes: The Case of Optogenetically Assisted Microbial Consortia

  2023cites this paper
• Toward Multiplexed Optogenetic Circuits

  2022cites this paper
• Optogenetic closed-loop feedback control of the unfolded protein response optimizes protein production

  2022cites this paper
• Cybergenetic control of microbial community composition

  2022cites this paper
• The bright frontiers of microbial metabolic optogenetics.

  2022cites this paper
• Optimal control and dynamic modulation of the ATPase gene expression for enforced ATP wasting in batch fermentations

  2022cites this paper
• Platforms for Optogenetic Stimulation and Feedback Control

  2022cites this paper
• Exploiting Information and Control Theory for Directing Gene Expression in Cell Populations

  2022cites this paper
• Optogenetic approaches in biotechnology and biomaterials.

  2022cites this paper
• Dynamical Models in Neuroscience From a Closed-Loop Control Perspective

  2022cites this paper
• Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production

  2022cites this paper
• A light tunable differentiation system for the creation and control of consortia in yeast

  2021cites this paper
• Reducing phenotypic instabilities of a microbial population during continuous cultivation based on cell switching dynamics

  2021cites this paper
• Maximizing batch fermentation efficiency by constrained model‐based optimization and predictive control of ATP turnover

  2021cites this paper
• Quorum sensing in synthetic biology: A review

  2021cites this paper
• Modular and Molecular Optimization of a LOV (Light–Oxygen–Voltage)-Based Optogenetic Switch in Yeast

  2021cites this paper
• Optogenetic Tools for Control of Public Goods in Saccharomyces cerevisiae

  2021cites this paper
• Advanced Optogenetic-Based Biosensing and Related Biomaterials

  2021cites this paper
• Optogenetic Control of Microbial Consortia Populations for Chemical Production.

  2021cites this paper
• The Neurospora crassa Inducible Q System Enables Simultaneous Optogenetic Amplification and Inversion in Saccharomyces cerevisiae for Bidirectional Control of Gene Expression.

  2021cites this paper
• Reducing phenotypic and genotypic instabilities of microbial population during continuous cultivation based on stochastic switching dynamics

  2021cites this paper
• Optogenetic tools for public goods control in Saccharomyces cerevisiae

  2021cites this paper
• Synthetic biology as driver for the biologization of materials sciences

  2021cites this paper
• Dynamical Modeling of Optogenetic Circuits in Yeast for Metabolic Engineering Applications.

  2021cites this paper
• The elusive relationship between structure and colour emission in beetle luciferases

  2020cites this paper
• Design and Characterization of Rapid Optogenetic Circuits for Dynamic Control in Yeast Metabolic Engineering.

  2020cites this paper
• The Promise of Optogenetics for Bioproduction: Dynamic Control Strategies and Scale-Up Instruments

  2020cites this paper
• Autonomous and Assisted Control for Synthetic Microbiology

  2020cites this paper