scholarly journals Toward Multiplexed Optogenetic Circuits

2022 ◽  
Vol 9 ◽  
Author(s):  
Ari Dwijayanti ◽  
Congqiang Zhang ◽  
Chueh Loo Poh ◽  
Thomas Lautier
Keyword(s):  
Large Range ◽  
Cellular Responses ◽  
Natural Light ◽  
Biotechnological Applications ◽  
Genetic Circuits ◽  
Dynamic Regulation ◽  
Potential Applications ◽  
Cellular Behaviors ◽  
Engineered Systems ◽  
Control Complex

Owing to its ubiquity and easy availability in nature, light has been widely employed to control complex cellular behaviors. Light-sensitive proteins are the foundation to such diverse and multilevel adaptive regulations in a large range of organisms. Due to their remarkable properties and potential applications in engineered systems, exploration and engineering of natural light-sensitive proteins have significantly contributed to expand optogenetic toolboxes with tailor-made performances in synthetic genetic circuits. Progressively, more complex systems have been designed in which multiple photoreceptors, each sensing its dedicated wavelength, are combined to simultaneously coordinate cellular responses in a single cell. In this review, we highlight recent works and challenges on multiplexed optogenetic circuits in natural and engineered systems for a dynamic regulation breakthrough in biotechnological applications.

Momordica balsamina L.: An Appraisal on Morphology, Ecological Diversity, Phytochemistry, Pharmacological and Biotechnological Applications

2020 ◽  
Vol 06 ◽  
Author(s):  
Saheed Sabiu ◽  
Christiana Eleojo Aruwa ◽  
Viresh Mohanlall ◽  
Himansu Baijnath
Keyword(s):  
Relevant Information ◽  
Perennial Herb ◽  
Biotechnological Applications ◽  
Tropical Regions ◽  
Toxicological Data ◽  
Human Disorders ◽  
Potential Applications ◽  
Baseline Information ◽  
The Caribbean ◽  
Bioactive Agents

Background: Momordica balsamina L. is a monoecious climbing vine and perennial herb native to the tropical regions of Asia, Arabia and the Caribbean, and with prominent presence in Nigeria, Botswana, Namibia, Swaziland and Southern African provinces. While evidence of its anecdotal usage as medicine exist, scientific reports complementing the claims are still emerging or at their infancy. Objective: This review appraised the morphology, therapeutic and biotechnological significance of M. balsamina. Method: Online resources such as Google Scholar, PubMed, ScienceDirect and MeSH were utilized for literature search and included relevant information from inception till May 2020 to streamline sought outcomes for in-depth discussion. Results: The data gathered and considered worthy of inclusion in this study revealed that M. balsamina is rich in phytonutrients of medicinal significance with cucurbitane-type triterpenoids, balsamin and momordins well characterized and fully elucidated. These compounds and other novel bioactive agents in M. balsamina have found remarkable pharmacological relevance and could further be harnessed for use against several debilitating human disorders. Conclusion: The potential applications of M. balsamina as nutraceutical and pharmaceutical agent should not be undermined. Also, with the inadequate toxicological data on this wild species, its consumption should be with caution and translational studies that could advance scientific knowledge and aid better understanding of both its pharmacokinetics and pharmacodynamics without sidelining its potent biotechnological applications are highly encouraged. It is hoped that this paper will provide baseline information that could serve as a guide and inspiration for further studies on the prospects of M. balsamina.

scholarly journals Properties of alternative microbial hosts used in synthetic biology: towards the design of a modular chassis

2016 ◽  
Vol 60 (4) ◽  
pp. 303-313 ◽  
Author(s):  
Juhyun Kim ◽  
Manuel Salvador ◽  
Elizabeth Saunders ◽  
Jaime González ◽  
Claudio Avignone-Rossa ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Genetic Information ◽  
Essential Element ◽  
Model Organisms ◽  
Biotechnological Applications ◽  
Cell Models ◽  
Genetic Circuits ◽  
Metabolic Diversity ◽  
Translational Machinery ◽  
Metabolic Fluxes

The chassis is the cellular host used as a recipient of engineered biological systems in synthetic biology. They are required to propagate the genetic information and to express the genes encoded in it. Despite being an essential element for the appropriate function of genetic circuits, the chassis is rarely considered in their design phase. Consequently, the circuits are transferred to model organisms commonly used in the laboratory, such as Escherichia coli, that may be suboptimal for a required function. In this review, we discuss some of the properties desirable in a versatile chassis and summarize some examples of alternative hosts for synthetic biology amenable for engineering. These properties include a suitable life style, a robust cell wall, good knowledge of its regulatory network as well as of the interplay of the host components with the exogenous circuits, and the possibility of developing whole-cell models and tuneable metabolic fluxes that could allow a better distribution of cellular resources (metabolites, ATP, nucleotides, amino acids, transcriptional and translational machinery). We highlight Pseudomonas putida, widely used in many different biotechnological applications as a prominent organism for synthetic biology due to its metabolic diversity, robustness and ease of manipulation.

scholarly journals Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Flurina Boehi ◽  
Patrick Manetsch ◽  
Michael O. Hottiger
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Cellular Responses ◽  
Dynamic Regulation ◽  
Post Translational Modifications ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Adp Ribosyltransferase ◽  
Cell Signaling Pathways

AbstractSignaling cascades provide integrative and interactive frameworks that allow the cell to respond to signals from its environment and/or from within the cell itself. The dynamic regulation of mammalian cell signaling pathways is often modulated by cascades of protein post-translational modifications (PTMs). ADP-ribosylation is a PTM that is catalyzed by ADP-ribosyltransferases and manifests as mono- (MARylation) or poly- (PARylation) ADP-ribosylation depending on the addition of one or multiple ADP-ribose units to protein substrates. ADP-ribosylation has recently emerged as an important cell regulator that impacts a plethora of cellular processes, including many intracellular signaling events. Here, we provide an overview of the interplay between the intracellular diphtheria toxin-like ADP-ribosyltransferase (ARTD) family members and five selected signaling pathways (including NF-κB, JAK/STAT, Wnt-β-catenin, MAPK, PI3K/AKT), which are frequently described to control or to be controlled by ADP-ribosyltransferases and how these interactions impact the cellular responses.

scholarly journals Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux in Bacillus subtilis

2019 ◽  
Vol 48 (2) ◽  
pp. 996-1009 ◽  
Author(s):  
Yaokang Wu ◽  
Taichi Chen ◽  
Yanfeng Liu ◽  
Rongzhen Tian ◽  
Xueqin Lv ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Metabolic Pathways ◽  
Metabolic Flux ◽  
Target Genes ◽  
Fine Tuning ◽  
Dual Control ◽  
Genetic Circuits ◽  
Dynamic Regulation ◽  
Batch Bioreactor ◽  
Acetoin Production

Abstract Dynamic regulation is an effective strategy for fine-tuning metabolic pathways in order to maximize target product synthesis. However, achieving dynamic and autonomous up- and down-regulation of the metabolic modules of interest simultaneously, still remains a great challenge. In this work, we created an autonomous dual-control (ADC) system, by combining CRISPRi-based NOT gates with novel biosensors of a key metabolite in the pathway of interest. By sensing the levels of the intermediate glucosamine-6-phosphate (GlcN6P) and self-adjusting the expression levels of the target genes accordingly with the GlcN6P biosensor and ADC system enabled feedback circuits, the metabolic flux towards the production of the high value nutraceutical N-acetylglucosamine (GlcNAc) could be balanced and optimized in Bacillus subtilis. As a result, the GlcNAc titer in a 15-l fed-batch bioreactor increased from 59.9 g/l to 97.1 g/l with acetoin production and 81.7 g/l to 131.6 g/l without acetoin production, indicating the robustness and stability of the synthetic circuits in a large bioreactor system. Remarkably, this self-regulatory methodology does not require any external level of control such as the use of inducer molecules or switching fermentation/environmental conditions. Moreover, the proposed programmable genetic circuits may be expanded to engineer other microbial cells and metabolic pathways.

scholarly journals Combining Genomics, Metabolome Analysis, and Biochemical Modelling to Understand Metabolic Networks

2001 ◽  
Vol 2 (3) ◽  
pp. 155-168 ◽  
Author(s):  
Oliver Fiehn
Keyword(s):  
Metabolic Networks ◽  
Analytical Techniques ◽  
Cellular Responses ◽  
Protein Profiling ◽  
Gene Products ◽  
Metabolome Analysis ◽  
Genome Sequences ◽  
Potential Applications ◽  
Analytical Approaches ◽  
Accurate Quantification

Now that complete genome sequences are available for a variety of organisms, the elucidation of gene functions involved in metabolism necessarily includes a better understanding of cellular responses upon mutations on all levels of gene products, mRNA, proteins, and metabolites. Such progress is essential since the observable properties of organisms – the phenotypes – are produced by the genotype in juxtaposition with the environment. Whereas much has been done to make mRNA and protein profiling possible, considerably less effort has been put into profiling the end products of gene expression, metabolites. To date, analytical approaches have been aimed primarily at the accurate quantification of a number of pre-defined target metabolites, or at producing fingerprints of metabolic changes without individually determining metabolite identities. Neither of these approaches allows the formation of an in-depth understanding of the biochemical behaviour within metabolic networks. Yet, by carefully choosing protocols for sample preparation and analytical techniques, a number of chemically different classes of compounds can be quantified simultaneously to enable such understanding. In this review, the terms describing various metabolite-oriented approaches are given, and the differences among these approaches are outlined. Metabolite target analysis, metabolite profiling, metabolomics, and metabolic fingerprinting are considered. For each approach, a number of examples are given, and potential applications are discussed.

Preface

2008 ◽  
Vol 80 (8) ◽  
pp. vi
Author(s):  
Francesco Nicotra ◽  
Mary Garson
Keyword(s):  
Bioorganic Chemistry ◽  
Drug Discovery ◽  
Organic Synthesis ◽  
Industrial Application ◽  
Drug Research ◽  
Bioinorganic Chemistry ◽  
Biotechnological Applications ◽  
Potential Applications ◽  
Chemistry Division ◽  
Novel Drug

In August 2007, IUPAC‚ Organic and Biomolecular Chemistry Division launched a combined Biomolecular-Biotechnology Symposium as a major component of the 41st IUPAC Congress in Turin, Italy. This four-day CHEM-BIO-TECH 2007 Symposium comprised IUPAC‚ 1st Symposium on Biotechnology held jointly with IUPAC‚ 8th Symposium on Bioorganic Chemistry, ISBOC-8.In designing the program, the goal was to focus on work at the interface of biotechnology and biomolecular chemistry from which many key industrial and academic advances have sprung. The program embraced topics ranging from novel drug discovery, biosynthesis, biocatalysis, and organic synthesis through artificial biomolecules and other emerging biotechnological applications. Attention was also devoted to industrial experience in drug research and in biotechnological productions.The special topics discussed during the symposium included:- natural products synthesis, biosynthesis, and isolation- industrial application of bioorganic chemistry and biotechnology- bioorganic and bioinorganic chemistry, biosynthesis, and biocatalysis- analytical methods applied to molecular recognitionThis issue of Pure and Applied Chemistry comprises a collection of 11 papers based upon the invited lectures delivered at CHEM-BIO-TECH 2007. It offers readers an enduring record of the representative scientific contributions announced during the symposium, in an area of interface between chemistry and biology of great interest and relevant potential applications.Francesco Nicotra and Mary GarsonConference Chair and Co-chair

scholarly journals Classification of lipolytic enzymes and their biotechnological applications in the pulping industry

2017 ◽  
Vol 63 (3) ◽  
pp. 179-192 ◽  
Author(s):  
L. Ramnath ◽  
B. Sithole ◽  
R. Govinden
Keyword(s):  
Fatty Acids ◽  
Paper Industry ◽  
Pulp And Paper Industry ◽  
Pulp And Paper ◽  
Biotechnological Applications ◽  
Lipolytic Enzymes ◽  
Prevention And Treatment ◽  
Potential Applications ◽  
Microbial Sources

In the pulp and paper industry, during the manufacturing process, the agglomeration of pitch particles (composed of triglycerides, fatty acids, and esters) leads to the formation of black pitch deposits in the pulp and on machinery, which impacts on the process and pulp quality. Traditional methods of pitch prevention and treatment are no longer feasible due to environmental impact and cost. Consequently, there is a need for more efficient and environmentally friendly approaches. The application of lipolytic enzymes, such as lipases and esterases, could be the sustainable solution to this problem. Therefore, an understanding of their structure, mechanism, and sources are essential. In this report, we review the microbial sources for the different groups of lipolytic enzymes, the differences between lipases and esterases, and their potential applications in the pulping industry.

scholarly journals Construction and Enhancement of a Minimal Genetic AND Logic Gate

2008 ◽  
Vol 75 (3) ◽  
pp. 637-642 ◽  
Author(s):  
Daniel J. Sayut ◽  
Yan Niu ◽  
Lianhong Sun
Keyword(s):  
Transcriptional Activation ◽  
Logic Gate ◽  
Cellular Responses ◽  
Genetic Networks ◽  
Intercellular Signaling ◽  
Cellular Phenotype ◽  
Genetic Circuits ◽  
Regulatory Circuit ◽  
Shed Light ◽  
Activate Gene

ABSTRACT The ability of genetic networks to integrate multiple inputs in the generation of cellular responses is critical for the adaptation of cellular phenotype to distinct environments and of great interest in the construction of complex artificial circuits. To develop artificial genetic circuits that can integrate intercellular signaling molecules and commonly used inducing agents, we have constructed an artificial genetic AND gate based on the P luxI quorum-sensing promoter and the lac repressor. The hybrid promoter exhibited reduced basal and induced expression levels but increased expression capacity, generating clear logical responses that could be described using a simple mathematical model. The model also predicted that the AND gate's logic could be improved by altering the properties of the LuxR transcriptional activator and, in particular, by increasing its rate of transcriptional activation. Following these predictions, we were able to improve the AND gate's logic by ∼1.5-fold using a LuxR mutant library generated by directed evolution, providing the first example of the use of mutant transcriptional activators to improve the logic of a complex regulatory circuit. In addition, detailed characterizations of the AND gate's responses shed light on how LuxR, LacI, and RNA polymerase interact to activate gene expression.

scholarly journals Gene variant space for biosensor-based dynamic regulation

2021 ◽  
pp. 485-491
Author(s):  
María Camarena ◽  
Yadira Boada ◽  
Jesús Picó ◽  
Pablo Carbonell
Keyword(s):  
Genetically Engineered ◽  
Dynamic Responses ◽  
Cell Protein ◽  
Gene Variants ◽  
Gene Variant ◽  
Genetic Circuits ◽  
Dynamic Regulation ◽  
Expression Efficiency ◽  
Cell Factories ◽  
A Cell

Inside a cell, protein, production and biosensor pathways can be genetically engineered within a dynamic regulation architecture that provides robustness to cell factories. Here we investigated how the selection of gene variants and their associated expression efficiency and kinetic parameters can lead to a wide diversity of dynamic responses in terms of protein or metabolite production. Results show that there is a trade-off between gene expression efficiency and pathway performance, and it can be eventually related to the evolutionary fingerprint of each gene variant. Therefore, the organism source of gene variants is a factor that needs to be considered in the design of dynamic regulation for genetic circuits.

scholarly journals Transcriptomic and metabolomic responses to carbon and nitrogen sources in Methylomicrobium album BG8

2021 ◽  
Author(s):  
Scott Sugden ◽  
Marina Lazic ◽  
Dominic Sauvageau ◽  
Lisa Y. Stein
Keyword(s):  
Value Added ◽  
Nitrogen Sources ◽  
Cellular Responses ◽  
Growth Media ◽  
Cellular Activity ◽  
Biotechnological Applications ◽  
Carbon And Nitrogen Sources ◽  
Carbon And Nitrogen ◽  
Advantages And Disadvantages ◽  
Methylomicrobium Album

ABSTRACTMethanotrophs use methane as their sole carbon and energy source and represent an attractive platform for converting single-carbon feedstocks into value-added compounds. Optimizing these species for biotechnological applications involves choosing an optimal growth substrate based on an understanding of cellular responses to different nutrients. Although many studies of methanotrophs have examined growth rate, yield, and central carbon flux in cultures grown with different carbon and nitrogen sources, few studies have examined more global cellular responses to different media. Here, we evaluated global transcriptomic and metabolomic profiles of Methylomicrobium album BG8 when grown with methane or methanol as the carbon source and nitrate or ammonium as the nitrogen source. We identified five key physiological changes during growth on methanol: M. album BG8 cultures upregulated transcripts for the Entner-Doudoroff and pentose phosphate pathways for sugar catabolism, produced more ribosomes, remodeled its phospholipid membrane, activated various stress response systems, and upregulated glutathione-dependent formaldehyde detoxification. When using ammonium, M. album BG8 upregulated haoAB hydroxylamine dehydrogenase and the overall central metabolic activity; whereas when using nitrate, cultures upregulated genes for nitrate assimilation and conversion. Overall, we identified several nutrient source-specific responses that could provide a valuable basis for future research on the biotechnological optimization of these species.IMPORTANCEMethanotrophs are gaining increasing interest for their biotechnological potential to convert single-carbon compounds into value-added products such as industrial chemicals, fuels, and bioplastics. Optimizing these species for biotechnological applications requires a detailed understanding of how cellular activity and metabolism varies across different growth substrates. Although each of the two most commonly used carbon sources (methane or methanol) and nitrogen sources (ammonium or nitrate) in methanotroph growth media have well-described advantages and disadvantages in an industrial context, their effects on global cellular activity remain poorly characterized. Here, we comprehensively describe the transcriptomic and metabolomic changes that characterize the growth of an industrially promising methanotroph strain on multiple combinations of carbon and nitrogen sources. Our results represent a more holistic evaluation of cellular activity than previous studies of core metabolic pathways and provide a valuable basis for the future biotechnological optimization of these species.

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