SynBio最新文献 - Book学术

Tropical Fruit Virus Resistance in the Era of Next-Generation Plant Breeding 下一代植物育种时代的热带水果抗病毒能力

SynBio Pub Date : 2024-07-08 DOI: 10.3390/synbio2030016

Marcella Silva Vieira, Rafael Lara Rezende Cabral, Luíza Favaratto, Laiane Silva Maciel, André da Silva Xavier, F. Zerbini, Patricia M. B. Fernandes

引用次数: 0

Efficient Stereoselective Biotransformation of Prochiral Carbonyls by Endophytic Fungi from Handroanthus impetiginosus 手掌蕨内生真菌对手性羰基化合物的高效立体选择性生物转化

SynBio Pub Date : 2024-07-05 DOI: 10.3390/synbio2030015

Valmore Henrique Pereira dos Santos, Monielly Vasconcellos Pereira de Souza, Maurício Moraes Victor, V. B. Riatto, E. Silva

{"title":"Efficient Stereoselective Biotransformation of Prochiral Carbonyls by Endophytic Fungi from Handroanthus impetiginosus","authors":"Valmore Henrique Pereira dos Santos, Monielly Vasconcellos Pereira de Souza, Maurício Moraes Victor, V. B. Riatto, E. Silva","doi":"10.3390/synbio2030015","DOIUrl":"https://doi.org/10.3390/synbio2030015","url":null,"abstract":"Endophytic microorganisms are promising sources for new biocatalysts as they must deal with their host plants’ chemicals by developing adaptative strategies, such as enzymatic pathways. As part of our efforts in selecting endophytic strains as biocatalysts, this study describes the screening of endophytic fungi isolated from Handroanthus impetiginosus leaves for selective bioreduction of Acetophenone. The bioreductions were monitored by chiral gas chromatography and conducted to the selection of the endophyte Talaromyces sp. H4 as capable of reducing acetophenone to (S)-1-phenylethanol in excellent conversion and enantiomeric excess rates. The influence of seven parameters on the stereoselective bioreduction of acetophenone by Talaromyces sp. H4 was studied: reaction time, inoculum charge, shaking, pH, temperature, substrate concentration, and co-solvent. The optimal conditions were then used to reduce substituted acetophenones and Acetophenone scale-up, which furnished (S)-1-Phenylethanol in 73% yield and 96% ee. The results highlight the endophytic fungus Talaromyces sp. H4 as an excellent biocatalyst for stereoselective reduction of prochiral carbonyls.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141676146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver 二甲双胍可降低肉碱生物合成受损和脂肪肝小鼠的血浆三酰甘油水平

SynBio Pub Date : 2024-07-03 DOI: 10.3390/synbio2030014

B. Bjørndal, Tra-My Thi Le, Elin Strand, Lise Madsen, Rolf K. Berge

{"title":"Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver","authors":"B. Bjørndal, Tra-My Thi Le, Elin Strand, Lise Madsen, Rolf K. Berge","doi":"10.3390/synbio2030014","DOIUrl":"https://doi.org/10.3390/synbio2030014","url":null,"abstract":"The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (p < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141683316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crafting Genetic Diversity: Unlocking the Potential of Protein Evolution 创造遗传多样性：释放蛋白质进化的潜力

SynBio Pub Date : 2024-04-07 DOI: 10.3390/synbio2020009

Vamsi Krishna Gali, K. L. Tee, T. S. Wong

{"title":"Crafting Genetic Diversity: Unlocking the Potential of Protein Evolution","authors":"Vamsi Krishna Gali, K. L. Tee, T. S. Wong","doi":"10.3390/synbio2020009","DOIUrl":"https://doi.org/10.3390/synbio2020009","url":null,"abstract":"Genetic diversity is the foundation of evolutionary resilience, adaptive potential, and the flourishing vitality of living organisms, serving as the cornerstone for robust ecosystems and the continuous evolution of life on Earth. The landscape of directed evolution, a powerful biotechnological tool inspired by natural evolutionary processes, has undergone a transformative shift propelled by innovative strategies for generating genetic diversity. This shift is fuelled by several factors, encompassing the utilization of advanced toolkits like CRISPR-Cas and base editors, the enhanced comprehension of biological mechanisms, cost-effective custom oligo pool synthesis, and the seamless integration of artificial intelligence and automation. This comprehensive review looks into the myriad of methodologies employed for constructing gene libraries, both in vitro and in vivo, categorized into three major classes: random mutagenesis, focused mutagenesis, and DNA recombination. The objectives of this review are threefold: firstly, to present a panoramic overview of recent advances in genetic diversity creation; secondly, to inspire novel ideas for further innovation in genetic diversity generation; and thirdly, to provide a valuable resource for individuals entering the field of directed evolution.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140733760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Saccharomyces cerevisiae as a Host for Chondroitin Production 以酿酒酵母为宿主生产软骨素

SynBio Pub Date : 2024-04-03 DOI: 10.3390/synbio2020008

Márcia R. Couto, Joana L. Rodrigues, Oscar Dias, Lígia R. Rodrigues

{"title":"Saccharomyces cerevisiae as a Host for Chondroitin Production","authors":"Márcia R. Couto, Joana L. Rodrigues, Oscar Dias, Lígia R. Rodrigues","doi":"10.3390/synbio2020008","DOIUrl":"https://doi.org/10.3390/synbio2020008","url":null,"abstract":"Chondroitin is a glycosaminoglycan that has gained widespread use in nutraceuticals and pharmaceuticals, mainly for treating osteoarthritis. Traditionally, it has been extracted from animal cartilage but recently, biotechnological processes have emerged as a commercial alternative to avoid the risk of viral or prion contamination and offer a vegan-friendly source. Typically, these methods involve producing the chondroitin backbone using pathogenic bacteria and then modifying it enzymatically through the action of sulfotransferases. Despite the challenges of expressing active sulfotransferases in bacteria, the use of eukaryotic microorganisms is still limited to a few works using Pichia pastoris. To create a safer and efficient biotechnological platform, we constructed a biosynthetic pathway for chondroitin production in S. cerevisiae as a proof-of-concept. Up to 125 mg/L and 200 mg/L of intracellular and extracellular chondroitin were produced, respectively. Furthermore, as genome-scale models are valuable tools for identifying novel targets for metabolic engineering, a stoichiometric model of chondroitin-producing S. cerevisiae was developed and used in optimization algorithms. Our research yielded several novel targets, such as uridine diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase (QRI1), glucosamine-6-phosphate acetyltransferase (GNA1), or N-acetylglucosamine-phosphate mutase (PCM1) overexpression, that might enhance chondroitin production and guide future experimental research to develop more efficient host organisms for the biotechnological production process.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140750130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of SynBio Tools for Pseudomonas chlororaphis: A Versatile Non-Pathogenic Bacterium Host 为绿假单胞菌（Pseudomonas chlororaphis）开发 SynBio 工具：多用途非致病细菌宿主

SynBio Pub Date : 2024-03-27 DOI: 10.3390/synbio2020007

Miguel Angel Bello-González, L. P. Bedoya-Perez, Miguel Alberto Pantoja-Zepeda, J. Utrilla

{"title":"Development of SynBio Tools for Pseudomonas chlororaphis: A Versatile Non-Pathogenic Bacterium Host","authors":"Miguel Angel Bello-González, L. P. Bedoya-Perez, Miguel Alberto Pantoja-Zepeda, J. Utrilla","doi":"10.3390/synbio2020007","DOIUrl":"https://doi.org/10.3390/synbio2020007","url":null,"abstract":"Pseudomonas chlororaphis ATCC 9446 is a non-pathogenic bacterium associated with the rhizosphere. It is commonly used as a biocontrol agent against agricultural pests. This organism can grow on a variety of carbon sources, has a robust secondary metabolism, and produces secondary metabolites with antimicrobial properties. This makes it an alternative host organism for synthetic biology applications. However, as a novel host there is a need for well-characterized molecular tools that allow fine control of gene expression and exploration of its metabolic potential. In this work we developed and characterized expression vectors for P. chlororaphis. We used two different promoters: the exogenously induced lac-IPTG promoter, and LuxR-C6-AHL, which we evaluated for its auto-inducible capacities, as well as using an external addition of C6-AHL. The expression response of these vectors to the inducer concentration was characterized by detecting a reporter fluorescent protein (YFP: yellow fluorescent protein). Furthermore, the violacein production operon was evaluated as a model heterologous pathway. We tested violacein production in shake flasks and a 3 L fermenter, showing that P. chlororaphis possesses a vigorous aromatic amino acid metabolism and was able to produce 1 g/L of violacein in a simple batch reactor experiment with minimal medium using only glucose as the carbon source. We compared the experimental results with the predictions of a modified genome scale model. The presented results show the potential of P. chlororaphis as a novel host organism for synthetic biology applications.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research 扩大生物合成工具箱：体外 II 型多酮苷合成酶研究的潜力与挑战

SynBio Pub Date : 2024-03-07 DOI: 10.3390/synbio2010006

Max A. J. Rivers, Andrew N. Lowell

{"title":"Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research","authors":"Max A. J. Rivers, Andrew N. Lowell","doi":"10.3390/synbio2010006","DOIUrl":"https://doi.org/10.3390/synbio2010006","url":null,"abstract":"Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140260635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pangenome-Scale Mathematical Modelling of ANAMMOX Bacteria Metabolism ANAMMOX 细菌代谢的泛基因组尺度数学建模

SynBio Pub Date : 2024-02-08 DOI: 10.3390/synbio2010005

Roman G. Bielski, M. A. Islam

{"title":"Pangenome-Scale Mathematical Modelling of ANAMMOX Bacteria Metabolism","authors":"Roman G. Bielski, M. A. Islam","doi":"10.3390/synbio2010005","DOIUrl":"https://doi.org/10.3390/synbio2010005","url":null,"abstract":"Removal of fixed nitrogen compounds such as ammonium and nitrite from wastewater is of critical importance for balancing the nitrogen cycle and protecting aquatic environments from eutrophication. ANaerobic AMMonium OXidising (ANAMMOX) bacteria have recently been employed for fixed nitrogen removal purposes in wastewater treatment processes. These specialised bacteria convert ammonium and nitrite into nitrogen gas anaerobically, thereby reducing the amount of energy required for aeration in conventional wastewater treatment processes. However, slow growth rates of ANAMMOX remain a major obstacle towards their widespread use in industrial wastewater treatment processes. Thus, a pangenome-scale, constraint-based metabolic model, iRB399, of ANAMMOX bacteria has been developed to design strategies for accelerating their growth. The main metabolic limitation was identified in the energy metabolism of these bacteria, concerning the production of ATP. The extremely low efficiency of the electron transport chain combined with very high growth-associated maintenance energy is likely to be responsible for the slow growth of ANAMMOX. However, different ANAMMOX species were found to conserve energy using a variety of different redox couples, and the modelling simulations revealed their comparative advantages under different growth conditions. iRB399 also identified dispensable catabolic reactions that have demonstrably beneficial effects on enhancing the growth rates of ANAMMOX bacteria. Thus, the pangenome-scale model will not only help identify and overcome metabolic limitations of ANNAMOX bacteria, but also provide a valuable resource for designing efficient ANNAMOX-based wastewater treatment processes.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139793074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pangenome-Scale Mathematical Modelling of ANAMMOX Bacteria Metabolism ANAMMOX 细菌代谢的泛基因组尺度数学建模

SynBio Pub Date : 2024-02-08 DOI: 10.3390/synbio2010005

Roman G. Bielski, M. A. Islam

{"title":"Pangenome-Scale Mathematical Modelling of ANAMMOX Bacteria Metabolism","authors":"Roman G. Bielski, M. A. Islam","doi":"10.3390/synbio2010005","DOIUrl":"https://doi.org/10.3390/synbio2010005","url":null,"abstract":"Removal of fixed nitrogen compounds such as ammonium and nitrite from wastewater is of critical importance for balancing the nitrogen cycle and protecting aquatic environments from eutrophication. ANaerobic AMMonium OXidising (ANAMMOX) bacteria have recently been employed for fixed nitrogen removal purposes in wastewater treatment processes. These specialised bacteria convert ammonium and nitrite into nitrogen gas anaerobically, thereby reducing the amount of energy required for aeration in conventional wastewater treatment processes. However, slow growth rates of ANAMMOX remain a major obstacle towards their widespread use in industrial wastewater treatment processes. Thus, a pangenome-scale, constraint-based metabolic model, iRB399, of ANAMMOX bacteria has been developed to design strategies for accelerating their growth. The main metabolic limitation was identified in the energy metabolism of these bacteria, concerning the production of ATP. The extremely low efficiency of the electron transport chain combined with very high growth-associated maintenance energy is likely to be responsible for the slow growth of ANAMMOX. However, different ANAMMOX species were found to conserve energy using a variety of different redox couples, and the modelling simulations revealed their comparative advantages under different growth conditions. iRB399 also identified dispensable catabolic reactions that have demonstrably beneficial effects on enhancing the growth rates of ANAMMOX bacteria. Thus, the pangenome-scale model will not only help identify and overcome metabolic limitations of ANNAMOX bacteria, but also provide a valuable resource for designing efficient ANNAMOX-based wastewater treatment processes.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139852992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic Investigation in CRISPR/Cas9-Mediated GRIK1-, GRIK2-, and GRIK4-Gene-Knockout Human Neuroblastoma Cells CRISPR/Cas9 介导的 GRIK1、GRIK2 和 GRIK4 基因敲除人神经母细胞瘤细胞的转录组研究

SynBio Pub Date : 2024-02-05 DOI: 10.3390/synbio2010004

Tsung-Ming Hu, Shih-Hsin Hsu, Hsin-Yao Tsai, M. Cheng

{"title":"Transcriptomic Investigation in CRISPR/Cas9-Mediated GRIK1-, GRIK2-, and GRIK4-Gene-Knockout Human Neuroblastoma Cells","authors":"Tsung-Ming Hu, Shih-Hsin Hsu, Hsin-Yao Tsai, M. Cheng","doi":"10.3390/synbio2010004","DOIUrl":"https://doi.org/10.3390/synbio2010004","url":null,"abstract":"The glutamate ionotropic kainate receptors, encoded by the GRIK gene family, are composed of four subunits and function as ligand-activated ion channels. They play a critical role in regulating synaptic transmission and various synaptic receptors’ processes, as well as in the pathophysiology of schizophrenia. However, their functions and mechanisms of action need to be better understood and are worthy of exploration. To further understand the exact role of the kainate receptors in vitro, we generated kainate-receptor-knockout (KO) isogenic SH-SY5Y cell lines using the CRISPR/Cas9-mediated gene editing method. We conducted RNA sequencing (RNA-seq) to determine the differentially expressed genes (DEGs) in the isogenic edited cells and used rhodamine-phalloidin staining to quantitate filamentous actin (F-actin) in differentiated edited cells. The RNA-seq and the Gene Ontology enrichment analysis revealed that the genetic deletion of the GRIK1, GRIK2, and GRIK4 genes disturbed multiple genes involved in numerous signal pathways, including a converging pathway related to the synaptic membrane. An enrichment analysis of gene–disease associations indicated that DEGs in the edited cell lines were associated with several neuropsychiatric disorders, especially schizophrenia. In the morphology study, fluorescent images show that less F-actin was expressed in differentiated SH-SY5Y cells with GRIK1, GRIK2, or GRIK4 deficiency than wild-type cells. Our data indicate that kainate receptor deficiency might disturb synaptic-membrane-associated genes, and elucidating these genes should shed some light on the pathophysiology of schizophrenia. Furthermore, the transcriptomic profiles for kainate receptor deficiency of SH-SY5Y cells contribute to emerging evidence for the novel mechanisms underlying the effect of kainate receptors and the pathophysiology of schizophrenia. In addition, our data suggest that kainate-receptor-mediated F-actin remodeling may be a candidate mechanism underlying schizophrenia.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139805239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0