Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.235
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Nat Commun ; 10(1): 2615, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197154

RESUMO

Balanced expression of multiple genes is central for establishing new biosynthetic pathways or multiprotein cellular complexes. Methods for efficient combinatorial assembly of regulatory sequences (promoters) and protein coding sequences are therefore highly wanted. Here, we report a high-throughput cloning method, called COMPASS for COMbinatorial Pathway ASSembly, for the balanced expression of multiple genes in Saccharomyces cerevisiae. COMPASS employs orthogonal, plant-derived artificial transcription factors (ATFs) and homologous recombination-based cloning for the generation of thousands of individual DNA constructs in parallel. The method relies on a positive selection of correctly assembled pathway variants from both, in vivo and in vitro cloning procedures. To decrease the turnaround time in genomic engineering, COMPASS is equipped with multi-locus CRISPR/Cas9-mediated modification capacity. We demonstrate the application of COMPASS by generating cell libraries producing ß-carotene and co-producing ß-ionone and biosensor-responsive naringenin. COMPASS will have many applications in synthetic biology projects that require gene expression balancing.


Assuntos
Vias Biossintéticas/genética , Engenharia Metabólica/métodos , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Técnicas Biossensoriais/métodos , Sistemas CRISPR-Cas/genética , Clonagem Molecular/métodos , Flavanonas/biossíntese , Recombinação Homóloga/genética , Norisoprenoides/biossíntese , Regiões Promotoras Genéticas/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Biologia Sintética/métodos , Fatores de Transcrição/genética , beta Caroteno/biossíntese
2.
Microb Cell Fact ; 18(1): 96, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142347

RESUMO

BACKGROUND: Promoter evolution by synthetic promoter library (SPL) is a powerful approach to development of functional synthetic promoters to synthetic biology. However, it requires much tedious and time-consuming screenings because of the plethora of different variants in SPL. Actually, a large proportion of mutants in the SPL are significantly lower in strength, which contributes only to fabrication of a promoter library with a continuum of strength. Thus, to effectively obtain the evolved synthetic promoter exhibiting higher strength, it is essential to develop novel strategies to construct mutant library targeting the pivotal region rather than the arbitrary region of the template promoter. In this study, a strategy termed stepwise evolution targeting the spacer of core promoter (SETarSCoP) was established in Bacillus subtilis to effectively evolve the strength of bacterial promoter. RESULTS: The native promoter, PsrfA, from B. subtilis, which exhibits higher strength than the strong promoter P43, was set as the parental template. According to the comparison of conservation of the spacer sequences between - 35 box and - 10 box among a set of strong and weak native promoter, it revealed that 7-bp sequence immediately upstream of the - 10 box featured in the regulation of promoter strength. Based on the conservative feature, two rounds of consecutive evolution were performed targeting the hot region of PsrfA. In the first round, a primary promoter mutation library (pPML) was constructed by mutagenesis targeting the 3-bp sequence immediately upstream of the - 10 box of the PsrfA. Subsequently, four evolved mutants from pPML were selected to construction of four secondary promoter mutation libraries (sPMLs) based on mutagenesis of the 4-bp sequence upstream of the first-round target. After the consecutive two-step evolution, the mutant PBH4 was identified and verified to be a highly evolved synthetic promoter. The strength of PBH4 was higher than PsrfA by approximately 3 times. Moreover, PBH4 also exhibited broad suitability for different cargo proteins, such as ß-glucuronidase and nattokinase. The proof-of-principle test showed that SETarSCoP successfully evolved both constitutive and inducible promoters. CONCLUSION: Comparing with the commonly used SPL strategy, SETarSCoP facilitates the evolution process to obtain strength-evolved synthetic bacterial promoter through fabrication and screening of small-scale mutation libraries. This strategy will be a promising method to evolve diverse bacterial promoters to expand the toolbox for synthetic biology.


Assuntos
Bacillus subtilis/genética , Evolução Molecular Direcionada/métodos , Regiões Promotoras Genéticas , Biblioteca Gênica , Mutagênese/genética , Mutação , Biologia Sintética/métodos
3.
J Microbiol ; 57(8): 637-643, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31079333

RESUMO

Bacteria sense and respond to the environment, communicate, and continuously interact with their surroundings, including host bodies. For more than a century, engineers have been trying to harness the natural ability of bacteria as live biotherapeutics for the treatment of diseases. Recent advances in synthetic biology facilitate the enlargement of the repertoire of genetic parts, tools, and devices that serve as a framework for biotherapy. This review describes bacterial species developed for specific diseases shown in in vitro studies and clinical stages. Here, we focus on drug delivery by programing bacteria and discuss the challenges for safety and improvement.


Assuntos
Bactérias/genética , Sistemas de Liberação de Medicamentos , Engenharia Genética/métodos , Biologia Sintética/métodos , Humanos
4.
Nat Commun ; 10(1): 2013, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043592

RESUMO

Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.


Assuntos
Sequência de Aminoácidos/genética , Regulação da Expressão Gênica , Engenharia de Proteínas/métodos , Proteólise , Biotecnologia/métodos , Células HEK293 , Meia-Vida , Células HeLa , Humanos , Microscopia Intravital/métodos , Células-Tronco Mesenquimais , Microscopia de Fluorescência , Biologia Sintética/métodos
5.
Appl Microbiol Biotechnol ; 103(13): 5143-5160, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31101942

RESUMO

Xylitol is a natural five-carbon sugar alcohol with potential for use in food and pharmaceutical industries owing to its insulin-independent metabolic regulation, tooth rehardening, anti-carcinogenic, and anti-inflammatory, as well as osteoporosis and ear infections preventing activities. Chemical and biosynthetic routes using D-xylose, glucose, or biomass hydrolysate as raw materials can produce xylitol. Among these methods, microbial production of xylitol has received significant attention due to its wide substrate availability, easy to operate, and eco-friendly nature, in contrast with high-energy consuming and environmental-polluting chemical method. Though great advances have been made in recent years for the biosynthesis of xylitol from xylose, glucose, and biomass hydrolysate, and the yield and productivity of xylitol are substantially improved by metabolic engineering and optimizing key metabolic pathway parameters, it is still far away from industrial-scale biosynthesis of xylitol. In contrary, the chemical synthesis of xylitol from xylose remains the dominant route. Economic and highly efficient xylitol biosynthetic strategies from an abundantly available raw material (i.e., glucose) by engineered microorganisms are on the hard way to forwarding. However, synthetic biology appears as a novel and promising approach to develop a super yeast strain for industrial production of xylitol from glucose. After a brief overview of chemical-based xylitol production, we critically analyzed and comprehensively summarized the major metabolic strategies used for the enhanced biosynthesis of xylitol in this review. Towards the end, the study is wrapped up with current challenges, concluding remarks, and future prospects for designing an industrial yeast strain for xylitol biosynthesis from glucose.


Assuntos
Microbiologia Industrial/economia , Engenharia Metabólica/economia , Engenharia Metabólica/métodos , Redes e Vias Metabólicas , Biologia Sintética/economia , Xilitol/biossíntese , Fermentação , Glucose/metabolismo , Microbiologia Industrial/métodos , Microbiologia Industrial/tendências , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Álcoois Açúcares/metabolismo , Biologia Sintética/métodos , Biologia Sintética/tendências , Xilose/metabolismo
6.
J Microbiol Biotechnol ; 29(5): 667-686, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31091862

RESUMO

Streptomyces are attractive microbial cell factories that have industrial capability to produce a wide array of bioactive secondary metabolites. However, the genetic potential of the Streptomyces species has not been fully utilized because most of their secondary metabolite biosynthetic gene clusters (SM-BGCs) are silent under laboratory culture conditions. In an effort to activate SM-BGCs encoded in Streptomyces genomes, synthetic biology has emerged as a robust strategy to understand, design, and engineer the biosynthetic capability of Streptomyces secondary metabolites. In this regard, diverse synthetic biology tools have been developed for Streptomyces species with technical advances in DNA synthesis, sequencing, and editing. Here, we review recent progress in the development of synthetic biology tools for the production of novel secondary metabolites in Streptomyces, including genomic elements and genome engineering tools for Streptomyces, the heterologous gene expression strategy of designed biosynthetic gene clusters in the Streptomyces chassis strain, and future directions to expand diversity of novel secondary metabolites.


Assuntos
Metabolismo Secundário , Streptomyces/genética , Streptomyces/metabolismo , Biologia Sintética/métodos , Produtos Biológicos/metabolismo , Regulação Bacteriana da Expressão Gênica , Engenharia Genética , Genoma Bacteriano , Família Multigênica , Metabolismo Secundário/genética
7.
Nat Commun ; 10(1): 2142, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086174

RESUMO

Metabolic engineers endeavor to create a bio-based manufacturing industry using microbes to produce fuels, chemicals, and medicines. Plant natural products (PNPs) are historically challenging to produce and are ubiquitous in medicines, flavors, and fragrances. Engineering PNP pathways into new hosts requires finding or modifying a suitable host to accommodate the pathway, planning and implementing a biosynthetic route to the compound, and discovering or engineering enzymes for missing steps. In this review, we describe recent developments in metabolic engineering at the level of host, pathway, and enzyme, and discuss how the field is approaching ever more complex biosynthetic opportunities.


Assuntos
Produtos Biológicos/metabolismo , Engenharia Metabólica/métodos , Microrganismos Geneticamente Modificados/metabolismo , Plantas/metabolismo , Vias Biossintéticas/genética , Enzimas/genética , Enzimas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Engenharia Metabólica/tendências , Microrganismos Geneticamente Modificados/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Biologia Sintética/métodos , Biologia Sintética/tendências
8.
Arch Microbiol ; 201(6): 855-862, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30929030

RESUMO

Synthetic biology, the design and synthesis of synthetic biological systems from DNA to whole cells, has provided us with the ultimate tools for space exploration and colonisation. Herein, we explore some of the most significant advances and future prospects in the field of synthetic biology, in the context of astrobiology and terraforming.


Assuntos
Exobiologia/tendências , Biologia Sintética/tendências , DNA/síntese química , DNA/genética , Exobiologia/métodos , Voo Espacial , Biologia Sintética/métodos
9.
J Biosci Bioeng ; 128(3): 355-364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30962099

RESUMO

To develop a remote control system of transgene expression through localized cellular heating of magnetic nanoparticles, a heat-inducible transgene expression system was introduced into mammalian cells. Cells were labeled with magnetic nanoparticles and exposed to an alternating magnetic field. The magnetically labeled cells expressed the transgene in a monolayer and multilayered cell sheets in which cells were heated around the magnetic nanoparticles without an apparent temperature increase in the culture medium. Magnetic cells were also generated by genetically engineering with a ferritin gene, and transgene expression could be induced by exposure to an alternating magnetic field. This approach may be applicable to the development of novel gene therapies in cell-based medicine.


Assuntos
Regulação da Expressão Gênica , Resposta ao Choque Térmico/genética , Temperatura Alta , Nanopartículas de Magnetita , Ativação Transcricional/efeitos dos fármacos , Transgenes , Animais , Ferritinas/genética , Ferritinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Células HeLa , Resposta ao Choque Térmico/efeitos dos fármacos , Calefação , Células Hep G2 , Humanos , Magnetismo , Biologia Sintética/métodos , Engenharia Tecidual/métodos , Transfecção/métodos , Transgenes/efeitos dos fármacos , Transgenes/genética
10.
Nat Nanotechnol ; 14(4): 369-378, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833694

RESUMO

Developing molecular communication platforms based on orthogonal communication channels is a crucial step towards engineering artificial multicellular systems. Here, we present a general and scalable platform entitled 'biomolecular implementation of protocellular communication' (BIO-PC) to engineer distributed multichannel molecular communication between populations of non-lipid semipermeable microcapsules. Our method leverages the modularity and scalability of enzyme-free DNA strand-displacement circuits to develop protocellular consortia that can sense, process and respond to DNA-based messages. We engineer a rich variety of biochemical communication devices capable of cascaded amplification, bidirectional communication and distributed computational operations. Encapsulating DNA strand-displacement circuits further allows their use in concentrated serum where non-compartmentalized DNA circuits cannot operate. BIO-PC enables reliable execution of distributed DNA-based molecular programs in biologically relevant environments and opens new directions in DNA computing and minimal cell technology.


Assuntos
Células Artificiais/citologia , Células Artificiais/metabolismo , Comunicação Celular , DNA/metabolismo , Biologia Sintética/métodos , Lógica , Transdução de Sinais
11.
Nat Rev Cancer ; 19(4): 187-195, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30837696

RESUMO

Engineered immune-cell-based cancer therapies have demonstrated robust efficacy in B cell malignancies, but challenges such as the lack of ideal targetable tumour antigens, tumour-mediated immunosuppression and severe toxicity still hinder their therapeutic efficacy and broad applicability. Synthetic biology can be used to overcome these challenges and create more robust, effective adaptive therapies that enable the specific targeting of cancer cells while sparing healthy cells. In this Progress article, we review recently developed gene circuit therapies for cancer using immune cells, nucleic acids and bacteria as chassis. We conclude by discussing outstanding challenges and future directions for realizing these gene circuit therapies in the clinic.


Assuntos
Neoplasias/genética , Neoplasias/terapia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Linfócitos B/patologia , Engenharia Celular/métodos , Redes Reguladoras de Genes , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Ácidos Nucleicos/genética , Biologia Sintética/métodos
12.
Nat Commun ; 10(1): 1053, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837474

RESUMO

With rapid progress in DNA synthesis and sequencing, strain engineering starts to be the rate-limiting step in synthetic biology. Here, we report a gRNA-tRNA array for CRISPR-Cas9 (GTR-CRISPR) for multiplexed engineering of Saccharomyces cerevisiae. Using reported gRNAs shown to be effective, this system enables simultaneous disruption of 8 genes with 87% efficiency. We further report an accelerated Lightning GTR-CRISPR that avoids the cloning step in Escherichia coli by directly transforming the Golden Gate reaction mix to yeast. This approach enables disruption of 6 genes in 3 days with 60% efficiency using reported gRNAs and 23% using un-optimized gRNAs. Moreover, we applied the Lightning GTR-CRISPR to simplify yeast lipid networks, resulting in a 30-fold increase in free fatty acid production in 10 days using just two-round deletions of eight previously identified genes. The GTR-CRISPR should be an invaluable addition to the toolbox of synthetic biology and automation.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , RNA Guia/genética , RNA de Transferência/genética , Saccharomyces cerevisiae/genética , Deleção de Sequência , Biologia Sintética/métodos , Fatores de Tempo
13.
Med Sci (Paris) ; 35(2): 181-186, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30774089

RESUMO

The eradication of infectious diseases is one of the oldest dreams of mankind. It has been materialized only once in History with smallpox in 1980. Considerable efforts are being developed against poliomyelitis viruses since 1988, but the ultimate goal of eradication is not yet achieved. Paradoxically, while the objective of having eradicated these two viral diseases is approaching, synthetic biology multiplies the prowesses of virus "neosynthesis", imperiling at least virtually the durability of these advances. This article emphasizes the potential of a new biology on one side, and the difficult reality of the fight against infections on the other.


Assuntos
Erradicação de Doenças/tendências , Controle de Infecções/tendências , Biologia Sintética , Viroses/prevenção & controle , Doenças Transmissíveis/epidemiologia , Erradicação de Doenças/história , Erradicação de Doenças/métodos , Saúde Global/história , História do Século XX , História do Século XXI , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Varíola/epidemiologia , Varíola/prevenção & controle , Biologia Sintética/história , Biologia Sintética/métodos , Biologia Sintética/normas , Biologia Sintética/tendências , Vacinação/história , Vacinação/métodos , Vacinação/tendências , Viroses/epidemiologia
14.
Methods Mol Biol ; 1927: 93-109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30788787

RESUMO

Efficient DNA assembly methods are essential tools for synthetic biology and metabolic engineering. Among several recently developed methods that allow assembly of multiple DNA fragments in a single step, DNA assembly using type IIS enzymes provides many advantages for complex pathway engineering. In particular, it provides the ability for the user to quickly assemble multigene constructs using a series of simple one-pot assembly steps starting from libraries of cloned and sequenced parts. We describe here a protocol for assembly of multigene constructs using the modular cloning system (MoClo). Making constructs using the MoClo system requires to first define the structure of the final construct to identify all basic parts and vectors required for the construction strategy. Basic parts that are not yet available need to be made. Multigene constructs are then assembled using a series of one-pot assembly steps with the set of identified parts and vectors.


Assuntos
Enzimas de Restrição do DNA/metabolismo , Engenharia Genética , Biologia Sintética , Clonagem Molecular , Ordem dos Genes , Engenharia Genética/métodos , Vetores Genéticos , Biologia Sintética/métodos , Transcrição Genética
16.
Plant Cell Physiol ; 60(6): 1184-1196, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715500

RESUMO

Microalgae constitute a highly diverse group of eukaryotic and photosynthetic microorganisms that have developed extremely efficient systems for harvesting and transforming solar energy into energy-rich molecules such as lipids. Although microalgae are considered to be one of the most promising platforms for the sustainable production of liquid oil, the oil content of these organisms is naturally low, and algal oil production is currently not economically viable. Chlamydomonas reinhardtii (Chlamydomonas) is an established algal model due to its fast growth, high transformation efficiency, and well-understood physiology and to the availability of detailed genome information and versatile molecular tools for this organism. In this review, we summarize recent advances in the development of genetic manipulation tools for Chlamydomonas, from gene delivery methods to state-of-the-art genome-editing technologies and fluorescent dye-based high-throughput mutant screening approaches. Furthermore, we discuss practical strategies and toolkits that enhance transgene expression, such as choice of expression vector and background strain. We then provide examples of how advanced genetic tools have been used to increase oil content in Chlamydomonas. Collectively, the current literature indicates that microalgal oil content can be increased by overexpressing key enzymes that catalyze lipid biosynthesis, blocking lipid degradation, silencing metabolic pathways that compete with lipid biosynthesis and modulating redox state. The tools and knowledge generated through metabolic engineering studies should pave the way for developing a synthetic biological approach to enhance lipid productivity in microalgae.


Assuntos
Chlamydomonas reinhardtii/genética , Engenharia Genética , Óleos Vegetais/metabolismo , Biologia Sintética/métodos , Chlamydomonas reinhardtii/metabolismo , Edição de Genes/métodos , Engenharia Genética/métodos
17.
Microb Biotechnol ; 12(2): 210-242, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30806035

RESUMO

The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and the ribosome construction machinery, behave as would behave a material implementation of the information-managing agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell's demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy-efficient way that is vastly better than our contemporary computers.


Assuntos
Fenômenos Fisiológicos Celulares , Modelos Biológicos , Biologia Sintética/métodos
19.
Nat Commun ; 10(1): 853, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787273

RESUMO

Cytosolic lipid droplets are endoplasmic reticulum-derived organelles typically found in seeds as reservoirs for physiological energy and carbon to fuel germination. Here, we report synthetic biology approaches to co-produce high-value sesqui- or diterpenoids together with lipid droplets in plant leaves. The formation of cytosolic lipid droplets is enhanced in the transient Nicotiana benthamiana system through ectopic production of WRINKLED1, a key regulator of plastid fatty acid biosynthesis, and a microalgal lipid droplet surface protein. Engineering of the pathways providing the universal C5-building blocks for terpenoids and installation of terpenoid biosynthetic pathways through direction of the enzymes to native and non-native compartments boost the production of target terpenoids. We show that anchoring of distinct biosynthetic steps onto the surface of lipid droplets leads to efficient production of terpenoid scaffolds and functionalized terpenoids. The co-produced lipid droplets "trap" the terpenoids in the cells.


Assuntos
Materiais Biocompatíveis/metabolismo , Citosol/metabolismo , Gotículas Lipídicas/metabolismo , Folhas de Planta/metabolismo , Terpenos/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Engenharia Metabólica/métodos , Microalgas/genética , Microalgas/metabolismo , Microscopia Confocal , Folhas de Planta/genética , Plantas Geneticamente Modificadas , Biologia Sintética/métodos , Tabaco/genética , Tabaco/metabolismo
20.
Microb Cell Fact ; 18(1): 35, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736778

RESUMO

During microbial applications, metabolic burdens can lead to a significant drop in cell performance. Novel synthetic biology tools or multi-step bioprocessing (e.g., fermentation followed by chemical conversions) are therefore needed to avoid compromised biochemical productivity from over-burdened cells. A possible solution to address metabolic burden is Division of Labor (DoL) via natural and synthetic microbial consortia. In particular, consolidated bioprocesses and metabolic cooperation for detoxification or cross feeding (e.g., vitamin C fermentation) have shown numerous successes in industrial level applications. However, distributing a metabolic pathway among proper hosts remains an engineering conundrum due to several challenges: complex subpopulation dynamics/interactions with a short time-window for stable production, suboptimal cultivation of microbial communities, proliferation of cheaters or low-producers, intermediate metabolite dilution, transport barriers between species, and breaks in metabolite channeling through biosynthesis pathways. To develop stable consortia, optimization of strain inoculations, nutritional divergence and crossing feeding, evolution of mutualistic growth, cell immobilization, and biosensors may potentially be used to control cell populations. Another opportunity is direct integration of non-bioprocesses (e.g., microbial electrosynthesis) to power cell metabolism and improve carbon efficiency. Additionally, metabolic modeling and 13C-metabolic flux analysis of mixed culture metabolism and cross-feeding offers a computational approach to complement experimental research for improved consortia performance.


Assuntos
Engenharia Metabólica/métodos , Redes e Vias Metabólicas , Consórcios Microbianos , Fermentação , Microbiologia Industrial , Análise do Fluxo Metabólico , Biologia Sintética/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA