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1.
Appl Microbiol Biotechnol ; 105(13): 5309-5324, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34215905

RESUMO

The xylose oxidative pathway (XOP) has been engineered in microorganisms for the production of a wide range of industrially relevant compounds. However, the performance of metabolically engineered XOP-utilizing microorganisms is typically hindered by D-xylonic acid accumulation. It acidifies the media and perturbs cell growth due to toxicity, thus curtailing enzymatic activity and target product formation. Fortunately, from the growing portfolio of genetic tools, several strategies that can be adapted for the generation of efficient microbial cell factories have been implemented to address D-xylonic acid accumulation. This review centers its discussion on the causes of D-xylonic acid accumulation and how to address it through different engineering and synthetic biology techniques with emphasis given on bacterial strains. In the first part of this review, the ability of certain microorganisms to produce and tolerate D-xylonic acid is also tackled as an important aspect in developing efficient microbial cell factories. Overall, this review could shed some insights and clarity to those working on XOP in bacteria and its engineering for the development of industrially applicable product-specialist strains. KEY POINTS: D-Xylonic acid accumulation is attributed to the overexpression of xylose dehydrogenase concomitant with basal or inefficient expression of enzymes involved in D-xylonic acid assimilation. Redox imbalance and insufficient cofactors contribute to D-xylonic acid accumulation. Overcoming D-xylonic acid accumulation can increase product formation among engineered strains. Engineering strategies involving enzyme engineering, evolutionary engineering, coutilization of different sugar substrates, and synergy of different pathways could potentially address D-xylonic acid accumulation.


Assuntos
Engenharia Metabólica , Xilose , Bactérias/genética , Meios de Cultura , Xilose/análogos & derivados
2.
Appl Microbiol Biotechnol ; 105(13): 5367-5381, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34196745

RESUMO

With the pursuit of natural non-calorie sweeteners, steviol glycosides (SGs) have become one of the most popular natural sweeteners in the market. The SGs in Stevia are a mixture of SGs synthesized from steviol (a terpenoid). SGs are diterpenoids. Different SGs depend on the number and position of sugar groups on the core steviol backbone. This diversity comes from the processing of glycoside steviol by various glycosyltransferases. Due to the differences in glycosylation, each SG has unique sensory properties. At present, it is more complicated to extract high-quality SGs from plants, so the excavation of the metabolic pathways of engineered microorganisms to synthesize SGs has been extensively studied. Specifically, the expression of different glycosyltransferases in microbes is key to the synthesis of various SGs by engineered microorganisms. To trigger more researches on the functional characterization of the enzymes encoded by these genes, this review describes the latest research progresses of the related enzymes involved in SG biosynthesis and metabolic engineering.Key points• Outlines the research progress of key enzymes in the biosynthetic pathway of SGs• Factors affecting the catalytic capacity of stevia glucosyltransferase• Provide guidance for the efficient synthesis of SGs in microbial cell factories.


Assuntos
Diterpenos do Tipo Caurano , Stevia , Glucosídeos , Glicosídeos , Glicosiltransferases/genética , Engenharia Metabólica , Folhas de Planta , Stevia/genética
3.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 1998-2009, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227290

RESUMO

Aromatic compounds make up a large part of fragrances and are traditionally produced by chemical synthesis and direct extraction from plants. Chemical synthesis depends on petroleum resources and has disadvantages such as causing environment pollutions and harsh reaction conditions. Due to the low content of aromatic compounds in plants and the low yield of direct extraction, plant extractions require large amounts of plant resources that occupy arable land. In recent years, with the development of metabolic engineering and synthetic biology, microbial synthesis of aromatic compounds from renewable resources has become a promising alternative approach to traditional methods. This review describes the research progress on the synthesis of aromatic fragrances by model microorganisms such as Escherichia coli or yeast, including the synthesis of vanillin through shikimic acid pathway and the synthesis of raspberry ketone through polyketide pathway. Moreover, this review highlights the elucidation of native biosynthesis pathways, the construction of synthetic pathways and metabolic regulation for the production of aromatic fragrances by microbial fermentation.


Assuntos
Engenharia Metabólica , Odorantes , Vias Biossintéticas , Ácido Chiquímico , Biologia Sintética
4.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2010-2025, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227291

RESUMO

Plant-derived aromatic natural products have important medicinal value and can be made into pharmaceutical and healthcare products with antibacterial, anti-inflammatory, analgesic, anti-oxidative, insecticidal and anthelmintic, expectorant and cough suppressant, tranquilizer and antitumor effects. However, the low content of aromatic natural products in plants and the difficulty and high costs in extraction and purification hampered its large-scale production and application. Recent advances in synthetic biology and metabolic engineering have enabled the tailor-made production of aromatic natural products using engineered microbial cell factories. This review summarizes the categories, the synthetic pathways, the key enzymes and the synthetic biology strategies for production of aromatic natural products, and discusses the challenges and opportunities in this area.


Assuntos
Produtos Biológicos , Biologia Sintética , Engenharia Metabólica , Plantas
5.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2050-2076, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227294

RESUMO

Plant polyphenols are phenylpropanoid derivatives including phenolic acids, stilbenes, curcumins and flavonoids. These compounds display a variety of biological and pharmacological activities such as antioxidation, vasorelaxation, anti-coagulation, anti-inflammation, anti-tumor and anti-virus, conferring a huge application potential in the sectors of drugs, foods, cosmetics, and chemicals. Microorganisms have become important hosts for heterologous synthesis of natural products due to the advantages of fast growth, easiness of culture and industrial operation. In recent years, the development of synthetic biology has boosted the microbial synthesis of plant natural products, achieving substantial progress. In this review, we summarize the synthesis of plant polyphenols in engineered Escherichia coli, Saccharomyces cerevisiae and other microorganisms equipped with the designed biosynthetic pathways of polyphenols. We also discuss the optimization strategies such as precursor engineering, dynamic regulation, and co-cultivation to improve the production of polyphenols and propose future prospects for polyphenol pathway engineering.


Assuntos
Engenharia Metabólica , Polifenóis , Vias Biossintéticas , Plantas , Saccharomyces cerevisiae/genética
6.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2085-2104, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227296

RESUMO

Terpenoids are a group of structurally diverse compounds with good biological activities and versatile functions such as anti-cancer and immunity-enhancing effects, and are widely used in food, healthcare and medical industries. Facilitated by the increasing understandings on the natural biosynthetic pathways of terpenoids in recent years, Saccharomyces cerevisiae has been engineered into high-yield strains for production of a variety of terpenoids, some of which have reached or become close to the level required by industrial production. In this connection, synthetic biology driven biotechnological production of terpenoids has become a promising alternative to chemical synthesis and traditional extraction approaches. This article summarizes the recent process in engineering S. cerevisiae for terpenoids biosynthesis, highlighting the effect of synthetic biology strategies by taking a couple of typical terpenoids as examples.


Assuntos
Engenharia Metabólica , Saccharomyces cerevisiae , Vias Biossintéticas , Saccharomyces cerevisiae/genética , Biologia Sintética , Terpenos
7.
Nat Commun ; 12(1): 3254, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059668

RESUMO

The capability to design microbiomes with predictable functions would enable new technologies for applications in health, agriculture, and bioprocessing. Towards this goal, we develop a model-guided approach to design synthetic human gut microbiomes for production of the health-relevant metabolite butyrate. Our data-driven model quantifies microbial interactions impacting growth and butyrate production separately, providing key insights into ecological mechanisms driving butyrate production. We use our model to explore a vast community design space using a design-test-learn cycle to identify high butyrate-producing communities. Our model can accurately predict community assembly and butyrate production across a wide range of species richness. Guided by the model, we identify constraints on butyrate production by high species richness and key molecular factors driving butyrate production, including hydrogen sulfide, environmental pH, and resource competition. In sum, our model-guided approach provides a flexible and generalizable framework for understanding and accurately predicting community assembly and metabolic functions.


Assuntos
Bactérias/metabolismo , Técnicas Bacteriológicas/métodos , Butiratos/metabolismo , Microbioma Gastrointestinal/fisiologia , Anaerobiose , Bactérias/genética , Bactérias/isolamento & purificação , Biologia Computacional , DNA Bacteriano/isolamento & purificação , Genoma Bacteriano , Humanos , Sulfeto de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Microbiologia Industrial/métodos , Engenharia Metabólica , Análise de Sequência de DNA
8.
New Phytol ; 231(2): 537-539, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132415
9.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066641

RESUMO

The production of aldehydes, highly reactive and toxic chemicals, brings specific challenges to biocatalytic processes. Absence of natural accumulation of aldehydes in microorganisms has led to a combination of in vitro and in vivo strategies for both, bulk and fine production. Advances in genetic and metabolic engineering and implementation of computational techniques led to the production of various enzymes with special requirements. Cofactor synthesis, post-translational modifications and structure engineering are applied to prepare active enzymes for one-step or cascade reactions. This review presents the highlights in biocatalytical production of aldehydes with the potential to shape future industrial applications.


Assuntos
Aldeídos/metabolismo , Biocatálise , Aldeídos/química , Técnicas Biossensoriais , Enzimas/metabolismo , Ligantes , Engenharia Metabólica
10.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1637-1658, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085447

RESUMO

Filamentous fungi are important industrial microorganisms that play important roles in the production of bio-based products such as organic acids, proteins and secondary metabolites. The development of metabolic engineering and its enabling techniques have greatly promoted the design, construction and application of filamentous fungal cell factories. This article systematically reviews the development of filamentous fungal cell factories constructed through metabolic engineering, and discusses the challenges and future perspectives for systems metabolic engineering of filamentous fungi.


Assuntos
Fungos , Engenharia Metabólica , Fungos/genética
11.
J Ind Microbiol Biotechnol ; 48(5-6)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34124750

RESUMO

Alkyl glycosides are well-characterized nonionic surfactants, and can be prepared by transglycosylation reactions with retaining GH1 glycosidases being normally used for this purpose. The produced alkyl glycosides can also be hydrolyzed by the glycosidase, and hence, the yields of alkyl glycosides can be too low for industrial use. To improve the transglycosylation-to-hydrolysis ratio for a ß-glucosidase from Thermotoga maritima (TmBglA) for the synthesis of alkyl glycoside, six mutants (N222F, N223C, N223Q, G224A, Y295F, and F414S) were produced. N222F, N223C, N223Q, G224A improved catalytic activity, F295Y and F414S are hydrolytically crippled with p-nitrophenol-ß-d-glucopyranoside (pNPG) as substrate with an 85 and 70-fold decrease in apparent kcat, respectively; N222F shows the highest kcat/km value for pNPG. The substrate selectivity altered from pNPG to pNP-ß-d-fucoside for N222F, F295Y, and F414S and from cellubiose to gentiobiose for N222F and F414S. Using pNPG (34 mM) and hexanol 80% (vol/vol), N222F, Y295F, and F414S synthesized hexyl-ß-glycoside (HG) yields of 84.7%, 50.9%, and 54.1%, respectively, HG increased from 14.49 (TmBglA) to 22.8 mM (N222F) at 2 hr by 57.42%. However, this higher transglycosylation effect depended on that three mutants creates an environment more suited for hexanol in the active site pocket, and consequently suppressed its HG hydrolysis.


Assuntos
Glicosídeos/biossíntese , Thermotoga maritima/enzimologia , Thermotoga maritima/genética , beta-Glucosidase/genética , beta-Glucosidase/metabolismo , Alquilação , Dissacarídeos/biossíntese , Glicosídeo Hidrolases/metabolismo , Hidrólise , Microbiologia Industrial , Cinética , Engenharia Metabólica , Modelos Moleculares , Mutagênese Sítio-Dirigida , Conformação Proteica , Especificidade por Substrato
12.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1471-1476, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085437

RESUMO

Metabolic engineering is the use of recombinant DNA technology, synthetic biology and genome editing to modify the cellular networks including metabolic, gene regulatory, and signaling networks of an organism. It can achieve the desirable goals such as enhanced production of metabolites, and improve the capability of biomanufacturing pharmaceuticals, biofuels and biochemicals as well as other biotechnology products. In order to comprehend the status of metabolic engineering in past 30 years, we published this special issue to review the progress and trends of metabolic engineering from the four aspects of overall development, key technologies, host engineering and product engineering, respectively, for laying the foundation for the further development of metabolic engineering.


Assuntos
Aniversários e Eventos Especiais , Engenharia Metabólica , Biocombustíveis , Biotecnologia , Biologia Sintética
13.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1477-1493, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085438

RESUMO

Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic research and China's competence in the area of metabolic engineering according to the data of papers published in SCI-indexed journals in the past 30 years. Subsequently, the article summarizes the development of systems biology methods and enabling technologies of synthetic biology and their applications in metabolic engineering in the past 10 years. Finally, the major challenges and future perspectives for the development of metabolic engineering are briefly discussed.


Assuntos
Engenharia Metabólica , Biologia Sintética , Biotecnologia , Indústrias , Biologia de Sistemas
14.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1494-1509, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085439

RESUMO

In 1990s, Bailey and Stephanopoulos put forward the concept of classic metabolic engineering, aiming to use DNA recombination technology to rewire metabolic network to achieve improved cell performance and increased target products. In the last 30 years since the birth of metabolic engineering, life science have flourished, and new disciplines such as genomics, systems biology and synthetic biology have emerged, injecting new connotations and vitality into the development of metabolic engineering. Classic metabolic engineering research has entered into an unprecedented stage of systems metabolic engineering. The application of synthetic biology tools and strategies, such as omics technology, genomic-scale metabolic model, parts assembly, circuits design, dynamic control, genome editing and many others, have greatly improved the design, build, and rewiring capabilities of complex metabolism. The intervention of machine learning and the combination of evolutionary engineering and metabolic engineering will further promote the development of systems metabolic engineering. This paper analyzes the development of metabolic engineering in the past 30 years and summarizes the novel theories, techniques, strategies, and applications of metabolic engineering that have emerged over the past 30 years.


Assuntos
Engenharia Metabólica , Biologia Sintética , Edição de Genes , Redes e Vias Metabólicas/genética , Biologia de Sistemas
15.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1510-1525, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085440

RESUMO

¹³C metabolic flux analysis (¹³C-MFA) enables the precise quantification of intracellular metabolic reaction rates by analyzing the distribution of mass isotopomers of proteinogenic amino acids or intracellular metabolites through ¹³C labeling experiments. ¹³C-MFA has received much attention as it can help systematically understand cellular metabolic characteristics, guide metabolic engineering design and gain mechanistic insights into pathophysiology. This article reviews the advances of ¹³C-MFA in the past 30 years and discusses its potential and future perspective, with a focus on its application in industrial biotechnology and biomedicine.


Assuntos
Engenharia Metabólica , Análise do Fluxo Metabólico , Aminoácidos , Isótopos de Carbono , Marcação por Isótopo , Modelos Biológicos
16.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1526-1540, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085441

RESUMO

Genome-scale metabolic network model (GSMM) is becoming an important tool for studying cellular metabolic characteristics, and remarkable advances in relevant theories and methods have been made. Recently, various constraint-based GSMMs that integrated genomic, transcriptomic, proteomic, and thermodynamic data have been developed. These developments, together with the theoretical breakthroughs, have greatly contributed to identification of target genes, systems metabolic engineering, drug discovery, understanding disease mechanism, and many others. This review summarizes how to incorporate transcriptomic, proteomic, and thermodynamic-constraints into GSMM, and illustrates the shortcomings and challenges of applying each of these methods. Finally, we illustrate how to develop and refine a fully integrated GSMM by incorporating transcriptomic, proteomic, and thermodynamic constraints, and discuss future perspectives of constraint-based GSMM.


Assuntos
Modelos Biológicos , Proteômica , Genoma/genética , Engenharia Metabólica , Redes e Vias Metabólicas/genética
17.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1541-1563, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085442

RESUMO

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.


Assuntos
Engenharia Metabólica , Biologia Sintética , Redes e Vias Metabólicas/genética
18.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1564-1577, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085443

RESUMO

As an important model industrial microorganism, Escherichia coli has been widely used in pharmaceutical, chemical industry and agriculture. In the past 30 years, a variety of new strategies and techniques, including artificial intelligence, gene editing, metabolic pathway assembly, and dynamic regulation have been used to design, construct, and optimize E. coli cell factories, which remarkably improved the efficiency for biotechnological production of chemicals. In this review, three key aspects for constructing E. coli cell factories, including pathway design, pathway assembly and regulation, and optimization of global cellular performance, are summarized. The technologies that have played important roles in metabolic engineering of E. coli, as well as their future applications, are discussed.


Assuntos
Inteligência Artificial , Escherichia coli , Escherichia coli/genética , Edição de Genes , Engenharia Metabólica , Redes e Vias Metabólicas/genética
19.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1578-1602, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085444

RESUMO

Since its birth in the early 1990s, metabolic engineering technology has gone 30 years rapid development. As one of the preferred chassis for metabolic engineering, S. cerevisiae cells have been engineered into microbial cell factories for the production of a variety of bulk chemicals and novel high value-added bioactive compounds. In recent years, synthetic biology, bioinformatics, machine learning and other technologies have also greatly contributed to the technological development and applications of metabolic engineering. This review summarizes the important technological development for metabolic engineering of S. cerevisiae in the past 30 years. Firstly, classical metabolic engineering tools and strategies were reviewed, followed by reviewing systems metabolic engineering and synthetic biology driven metabolic engineering approaches. The review is concluded with discussing future perspectives for metabolic engineering of S. cerevisiae in the light of state-of-the-art technological development.


Assuntos
Engenharia Metabólica , Saccharomyces cerevisiae , Biologia Computacional , Saccharomyces cerevisiae/genética , Biologia Sintética
20.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1603-1618, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085445

RESUMO

Corynebacterium glutamicum is an important workhorse of industrial biotechnology, especially for amino acid bioindustry. This bacterium is being used to produce various amino acids at a level of over 6 million tons per year. In recent years, enabling technologies for C. glutamicum metabolic engineering have been developed and improved, which accelerated construction and optimization of microbial cell factoriers, expanding spectra of substrates and products, and facilitated basic researches on C. glutamicum. With these technologies, C. glutamicum has become one of the ideal microbial chasses. This review summarizes recent key technological developments of enabling technologies for C. glutamicum metabolic engineering and focuses on establishment and applications of CRISPR-based genome editing, gene expression regulation, adaptive laboratory evolution, and biosensor technologies.


Assuntos
Corynebacterium glutamicum , Aminoácidos , Biotecnologia , Corynebacterium glutamicum/genética , Edição de Genes , Engenharia Metabólica
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