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      Synthetic Biology Tools to Engineer Microbial Communities for Biotechnology

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          Abstract

          Microbial consortia have been used in biotechnology processes, including fermentation, waste treatment, and agriculture, for millennia. Today, synthetic biologists are increasingly engineering microbial consortia for diverse applications, including the bioproduction of medicines, biofuels, and biomaterials from inexpensive carbon sources. An improved understanding of natural microbial ecosystems, and the development of new tools to construct synthetic consortia and program their behaviors, will vastly expand the functions that can be performed by communities of interacting microorganisms. Here, we review recent advancements in synthetic biology tools and approaches to engineer synthetic microbial consortia, discuss ongoing and emerging efforts to apply consortia for various biotechnological applications, and suggest future applications.

          Highlights

          Microbial consortia exhibit advantages over monocultures, including division of labor, spatial organization, and robustness to perturbations.

          Synthetic biology tools are used to construct and control consortia by manipulating communication networks, regulating gene expression via exogenous inputs, and engineering syntrophic interactions.

          Synthetic biology approaches to control the behaviors of individual species within a consortium include population control, distribution of tasks, and spatial organization.

          Constructing microbial consortia is enhanced by computational models, which can predict preferred metabolic cross-feeding networks and infer population dynamics over time.

          Microbial biotechnology benefits from consortia due to the unique catalytic activities of each member, their ability to use complex substrates, compartmentalization of pathways, and distribution of molecular burden.

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          Most cited references88

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          Bacterial quorum-sensing network architectures.

          Quorum sensing is a cell-cell communication process in which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density. Quorum sensing allows bacteria to synchronize the gene expression of the group, and thus act in unison. Here, we review the mechanisms involved in quorum sensing with a focus on the Vibrio harveyi and Vibrio cholerae quorum-sensing systems. We discuss the differences between these two quorum-sensing systems and the differences between them and other paradigmatic bacterial signal transduction systems. We argue that the Vibrio quorum-sensing systems are optimally designed to precisely translate extracellular autoinducer information into internal changes in gene expression. We describe how studies of the V. harveyi and V. cholerae quorum-sensing systems have revealed some of the fundamental mechanisms underpinning the evolution of collective behaviors.
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            CRISPR/Cas9 in Genome Editing and Beyond

            The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.
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              Synthetic biology: applications come of age

              Key Points Early synthetic biology designs, namely the genetic toggle switch and repressilator, showed that regulatory components can be characterized and assembled to bring about complex, electronics-inspired behaviours in living systems (for example, memory storage and timekeeping). Through the characterization and assembly of genetic parts and biological building blocks, many more devices have been constructed, including switches, memory elements, oscillators, pulse generators, digital logic gates, filters and communication modules. Advances in the field are now allowing expansion beyond small gene networks to the realm of larger biological programs, which hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials. Synthetic biosensing circuits consist of sensitive elements that bind analytes and transducer modules that mobilize cellular responses. Balancing these two modules involves engineering modularity and specificity into the various circuits. Biosensor sensitive elements include environment-responsive promoters (transcriptional), RNA aptamers (translational) and protein receptors (post-translational). Biosensor transducer modules include engineered gene networks (transcriptional), non-coding regulatory RNAs (translational) and protein signal-transduction circuits (post-translational). The contributions of synthetic biology to therapeutics include: engineered networks and organisms for disease-mechanism elucidation, drug-target identification, drug-discovery platforms, therapeutic treatment, therapeutic delivery, and drug production and access. In the microbial production of biofuels and pharmaceuticals, synthetic biology has supplemented traditional genetic and metabolic engineering efforts by aiding the construction of optimized biosynthetic pathways. Optimizing metabolic flux through biosynthetic pathways is traditionally accomplished by driving the expression of pathway enzymes with strong, inducible promoters. New synthetic approaches include the rapid diversification of various pathway components, the rational and model-guided assembly of pathway components, and hybrid solutions.
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                Author and article information

                Contributors
                Journal
                Trends Biotechnol
                Trends Biotechnol
                Trends in Biotechnology
                Elsevier Science Publishers
                0167-7799
                1879-3096
                1 February 2019
                February 2019
                : 37
                : 2
                : 181-197
                Affiliations
                [1 ]Imperial College Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK
                [2 ]Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
                Author notes
                Article
                S0167-7799(18)30312-3
                10.1016/j.tibtech.2018.11.002
                6340809
                30497870
                d46afc8c-254a-4056-95d6-c4e40a42cb3c
                Crown Copyright © 2018 Published by Elsevier Ltd. All rights reserved.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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                Categories
                Article

                Biotechnology
                microbial consortia,synthetic biology,bioproduction,biomaterials,synthetic microbial communities,synthetic consortia

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