The Experts below are selected from a list of 33909 Experts worldwide ranked by ideXlab platform
Sang Yup Lee - One of the best experts on this subject based on the ideXlab platform.
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synthetic biology and Metabolic Engineering of actinomycetes for natural product discovery
Biotechnology Advances, 2019Co-Authors: E Palazzotto, Sang Yup Lee, Yaojun Tong, Tilmann WeberAbstract:Actinomycetes are one of the most valuable sources of natural products with industrial and medicinal importance. After more than half a century of exploitation, it has become increasingly challenging to find novel natural products with useful properties as the same known compounds are often repeatedly re-discovered when using traditional approaches. Modern genome mining approaches have led to the discovery of new biosynthetic gene clusters, thus indicating that actinomycetes still harbor a huge unexploited potential to produce novel natural products. In recent years, innovative synthetic biology and Metabolic Engineering tools have greatly accelerated the discovery of new natural products and the Engineering of actinomycetes. In the first part of this review, we outline the successful application of Metabolic Engineering to optimize natural product production, focusing on the use of multi-omics data, genome-scale Metabolic models, rational approaches to balance precursor pools, and the Engineering of regulatory genes and regulatory elements. In the second part, we summarize the recent advances of synthetic biology for actinomycetal Metabolic Engineering including cluster assembly, cloning and expression, CRISPR/Cas9 technologies, and chassis strain development for natural product overproduction and discovery. Finally, we describe new advances in reprogramming biosynthetic pathways through polyketide synthase and non-ribosomal peptide synthetase Engineering. These new developments are expected to revitalize discovery and development of new natural products with medicinal and other industrial applications.
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systems Metabolic Engineering strategies integrating systems and synthetic biology with Metabolic Engineering
Trends in Biotechnology, 2019Co-Authors: Kyeong Rok Choi, Woo Dae Jang, Dongsoo Yang, Jae Sung Cho, D Park, Sang Yup LeeAbstract:Metabolic Engineering allows development of microbial strains efficiently producing chemicals and materials, but it requires much time, effort, and cost to make the strains industrially competitive. Systems Metabolic Engineering, which integrates tools and strategies of systems biology, synthetic biology, and evolutionary Engineering with traditional Metabolic Engineering, has recently been used to facilitate development of high-performance strains. The past decade has witnessed this interdisciplinary strategy continuously being improved toward the development of industrially competitive overproducer strains. In this article, current trends in systems Metabolic Engineering including tools and strategies are reviewed, focusing on recent developments in selection of host strains, Metabolic pathway reconstruction, tolerance enhancement, and Metabolic flux optimization. Also, future challenges and prospects are discussed.
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toward systems Metabolic Engineering of streptomycetes for secondary metabolites production
Biotechnology Journal, 2018Co-Authors: Helene Lunde Robertsen, Tilmann Weber, Hyun Uk Kim, Sang Yup LeeAbstract:Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical trials in the last decades. A paradigm shift took place when the first whole genome sequences of streptomycetes became available, from which silent or "cryptic" biosynthetic gene clusters (BGCs) were discovered. Cryptic BGCs reveal a so far untapped potential of the microorganisms for the production of novel compounds, which has spurred new efforts in understanding the complex regulation between primary and secondary metabolism. This new trend has been accompanied with development of new computational resources (genome and compound mining tools), generation of various high-quality omics data, establishment of molecular tools, and other strain Engineering strategies. They all come together to enable systems Metabolic Engineering of streptomycetes, allowing more systematic and efficient strain development. In this review, the authors present recent progresses within systems Metabolic Engineering of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites.
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Metabolic Engineering for the microbial production of marine bioactive compounds
Biotechnology Advances, 2017Co-Authors: Xiangzhao Mao, Jianan Sun, Zhen Liu, Sang Yup LeeAbstract:Many marine bioactive compounds have medicinal and nutritional values. These bioactive compounds have been prepared using solvent-based extraction from marine bio-resources or chemical synthesis, which are costly, inefficient with low yields, and environmentally unfriendly. Recent advances in Metabolic Engineering allowed to some extent more efficient production of these compounds, showing promises to meet the increasing demand of marine natural bioactive compounds. In this paper, we review the strategies and statuses of Metabolic Engineering applied to microbial production of marine natural bioactive compounds including terpenoids and their derivatives, omega-3 polyunsaturated fatty acids, and marine natural drugs, and provide perspectives.
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Metabolic Engineering for the production of hydrocarbon fuels
Current Opinion in Biotechnology, 2015Co-Authors: Sang Yup Lee, Hye Mi Kim, Seungwoo CheonAbstract:Biofuels have been attracting increasing attention to provide a solution to the problems of climate change and our dependence on limited fossil oil. During the last decade, Metabolic Engineering has been performed to develop superior microorganisms for the production of so called advanced biofuels. Among the advanced biofuels, hydrocarbons possess high-energy content and superior fuel properties to other biofuels, and thus have recently been attracting much research interest. Here we review the recent advances in the microbial production of hydrocarbon fuels together with the Metabolic Engineering strategies employed to develop their production strains. Strategies employed for the production of long-chain and short-chain hydrocarbons derived from fatty acid metabolism along with the isoprenoid-derived hydrocarbons are reviewed. Also, the current limitations and future prospects in hydrocarbon-based biofuel production are discussed.
Jens Nielsen - One of the best experts on this subject based on the ideXlab platform.
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advancing Metabolic Engineering through systems biology of industrial microorganisms
Current Opinion in Biotechnology, 2015Co-Authors: Jens NielsenAbstract:Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic Engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for Metabolic Engineering. Here we review the application of systems biology tools for the identification of Metabolic Engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing Metabolic Engineering further.
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impact of synthetic biology and Metabolic Engineering on industrial production of fine chemicals
Biotechnology Advances, 2015Co-Authors: David Jullesson, Florian David, Jens Nielsen, Brian F PflegerAbstract:© 2015 Elsevier Inc. Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through Metabolic Engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key Metabolic Engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes.
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Impact of synthetic biology and Metabolic Engineering on industrial production of fine chemicals
Biotechnology Advances, 2015Co-Authors: David Jullesson, Brian Pfleger, Florian David, Jens NielsenAbstract:Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through Metabolic Engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key Metabolic Engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes.
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applications of computational modeling in Metabolic Engineering of yeast
Fems Yeast Research, 2014Co-Authors: Eduard J Kerkhoven, Petrijaan Lahtvee, Jens NielsenAbstract:Generally, a microorganism's phenotype can be described by its pattern of Metabolic fluxes. Although fluxes cannot be measured directly, inference of fluxes is well established. In biotechnology the aim is often to increase the capacity of specific fluxes. For this, Metabolic Engineering methods have been developed and applied extensively. Many of these rely on balancing of intracellular metabolites, redox, and energy fluxes, using genome-scale models (GEMs) that in combination with appropriate objective functions and constraints can be used to predict potential gene targets for obtaining a preferred flux distribution. These methods point to strategies for altering gene expression; however, fluxes are often controlled by post-transcriptional events. Moreover, GEMs are usually not taking into account Metabolic regulation, thermodynamics and enzyme kinetics. To facilitate Metabolic Engineering, tools from synthetic biology have emerged, enabling integration and assembly of naturally nonexistent, but well-characterized components into a living organism. To describe these systems kinetic models are often used and to integrate these systems with the standard Metabolic Engineering approach, it is necessary to expand the modeling of metabolism to consider kinetics of individual processes. This review will give an overview about models available for Metabolic Engineering of yeast and discusses their applications.
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Metabolic Engineering of yeast for production of fuels and chemicals
Current Opinion in Biotechnology, 2013Co-Authors: Jens Nielsen, Antonius J A Van Maris, Christer Larsson, Jack T PronkAbstract:Microbial production of fuels and chemicals from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. The yeast Saccharomyces cerevisiae offers many advantages as a platform cell factory for such applications. Already applied on a huge scale for bioethanol production, this yeast is easy to genetically engineer, its physiology, metabolism and genetics have been intensively studied and its robustness enables it to handle harsh industrial conditions. Introduction of novel pathways and optimization of its native cellular processes by Metabolic Engineering are rapidly expanding its range of cell-factory applications. Here we review recent scientific progress in Metabolic Engineering of S. cerevisiae for the production of bioethanol, advanced biofuels, and chemicals.
Hal S. Alper - One of the best experts on this subject based on the ideXlab platform.
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Metabolic Engineering of microbial cell factories for production of nutraceuticals
Microbial Cell Factories, 2019Co-Authors: Shuo-fu Yuan, Hal S. AlperAbstract:Metabolic Engineering allows for the rewiring of basic metabolism to overproduce both native and non-native metabolites. Among these biomolecules, nutraceuticals have received considerable interest due to their health-promoting or disease-preventing properties. Likewise, microbial Engineering efforts to produce these value-added nutraceuticals overcome traditional limitations of low yield from extractions and complex chemical syntheses. This review covers current strategies of Metabolic Engineering employed for the production of a few key nutraceuticals with selecting polyunsaturated fatty acids, polyphenolic compounds, carotenoids and non-proteinogenic amino acids as exemplary molecules. We focus on the use of both mono-culture and co-culture strategies to produce these molecules of interest. In each of these cases, Metabolic Engineering efforts are enabling rapid production of these molecules.
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Metabolic Engineering in the host yarrowia lipolytica
Metabolic Engineering, 2018Co-Authors: A M Abdelmawgoud, Kelly A Markham, Nian Liu, Claire M Palmer, Hal S. AlperAbstract:The nonconventional, oleaginous yeast, Yarrowia lipolytica is rapidly emerging as a valuable host for the production of a variety of both lipid and nonlipid chemical products. While the unique genetics of this organism pose some challenges, many new Metabolic Engineering tools have emerged to facilitate improved genetic manipulation in this host. This review establishes a case for Y. lipolytica as a premier Metabolic Engineering host based on innate Metabolic capacity, emerging synthetic tools, and Engineering examples. The metabolism underlying the lipid accumulation phenotype of this yeast as well as high flux through acyl-CoA precursors and the TCA cycle provide a favorable Metabolic environment for expression of relevant heterologous pathways. These properties allow Y. lipolytica to be successfully engineered for the production of both native and nonnative lipid, organic acid, sugar and acetyl-CoA derived products. Finally, this host has unique Metabolic pathways enabling growth on a wide range of carbon sources, including waste products. The expansion of carbon sources, together with the improvement of tools as highlighted here, have allowed this nonconventional organism to act as a cellular factory for valuable chemicals and fuels.
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Metabolic Engineering of strains from industrial scale to lab scale chemical production
Journal of Industrial Microbiology & Biotechnology, 2015Co-Authors: Hal S. AlperAbstract:A plethora of successful Metabolic Engineering case studies have been published over the past several decades. Here, we highlight a collection of microbially produced chemicals using a historical framework, starting with titers ranging from industrial scale (more than 50 g/L), to medium-scale (5–50 g/L), and lab-scale (0–5 g/L). Although engineered Escherichia coli and Saccharomyces cerevisiae emerge as prominent hosts in the literature as a result of well-developed genetic Engineering tools, several novel native-producing strains are gaining attention. This review catalogs the current progress of Metabolic Engineering towards production of compounds such as acids, alcohols, amino acids, natural organic compounds, and others.
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Draft Genome Sequence of the Oleaginous Yeast Yarrowia lipolytica PO1f, a Commonly Used Metabolic Engineering Host.
Genome announcements, 2014Co-Authors: Leqian Liu, Hal S. AlperAbstract:ABSTRACT The draft genome sequence of the oleaginous yeast Yarrowia lipolytica stain PO1f, a commonly used Metabolic Engineering host, is presented here. The approximately 20.3-Mb genome sequence of PO1f will greatly facilitate research efforts in Metabolic Engineering of Yarrowia lipolytica for value-added chemical production.
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expanding the Metabolic Engineering toolbox more options to engineer cells
Trends in Biotechnology, 2007Co-Authors: Keith E J Tyo, Hal S. Alper, Gregory StephanopoulosAbstract:Metabolic Engineering exploits an integrated, systems-level approach for optimizing a desired cellular property or phenotype; and great strides have been made within this scope and context during the past fifteen years. However, due to limitations in the concepts and techniques, these have relied on a focused, pathway-oriented view. Recent advances in ‘omics’ technologies and computational systems biology have brought the foundational systems approach of Metabolic Engineering into focus. At the same time, protein Engineering and synthetic biology have expanded the breadth and precision of the methods available to Metabolic engineers to improve strain properties. Examples are presented that illustrate this broader perspective of tools and concepts, including a recent approach for global transcriptional machinery Engineering (gTME), which has demonstrated the ability to elicit multigenic transcriptional changes that have improved phenotypes compared with single-gene perturbations.
Huimin Zhao - One of the best experts on this subject based on the ideXlab platform.
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advancing Metabolic Engineering of saccharomyces cerevisiae using the crispr cas system
Biotechnology Journal, 2018Co-Authors: Jiazhang Lian, Mohammad Hamedirad, Huimin ZhaoAbstract:Thanks to its ease of use, modularity, and scalability, the clustered regularly interspaced short palindromic repeats (CRISPR) system has been increasingly used in the design and Engineering of Saccharomyces cerevisiae, one of the most popular hosts for industrial biotechnology. This review summarizes the recent development of this disruptive technology for Metabolic Engineering applications, including CRISPR-mediated gene knock-out and knock-in as well as transcriptional activation and interference. More importantly, multi-functional CRISPR systems that combine both gain- and loss-of-function modulations for combinatorial Metabolic Engineering are highlighted.
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combinatorial Metabolic Engineering using an orthogonal tri functional crispr system
Nature Communications, 2017Co-Authors: Mohammad Hamedirad, Jiazhang Lian, Sumeng Hu, Huimin ZhaoAbstract:Designing an optimal microbial cell factory often requires overexpression, knock-down, and knock-out of multiple gene targets. Unfortunately, such rewiring of cellular metabolism is often carried out sequentially and with low throughput. Here, we report a combinatorial Metabolic Engineering strategy based on an orthogonal tri-functional CRISPR system that combines transcriptional activation, transcriptional interference, and gene deletion (CRISPR-AID) in the yeast Saccharomyces cerevisiae. This strategy enables perturbation of the Metabolic and regulatory networks in a modular, parallel, and high-throughput manner. We demonstrate the application of CRISPR-AID not only to increase the production of β-carotene by 3-fold in a single step, but also to achieve 2.5-fold improvement in the display of an endoglucanase on the yeast surface by optimizing multiple Metabolic Engineering targets in a combinatorial manner.
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Metabolic Engineering of Oleaginous Yeasts for Production of Fuels and Chemicals
Frontiers Media S.A., 2017Co-Authors: Shuobo Shi, Huimin ZhaoAbstract:Oleaginous yeasts have been increasingly explored for production of chemicals and fuels via Metabolic Engineering. Particularly, there is a growing interest in using oleaginous yeasts for the synthesis of lipid-related products due to their high lipogenesis capability, robustness, and ability to utilize a variety of substrates. Most of the Metabolic Engineering studies in oleaginous yeasts focused on Yarrowia that already has plenty of genetic Engineering tools. However, recent advances in systems biology and synthetic biology have provided new strategies and tools to engineer those oleaginous yeasts that have naturally high lipid accumulation but lack genetic tools, such as Rhodosporidium, Trichosporon, and Lipomyces. This review highlights recent accomplishments in Metabolic Engineering of oleaginous yeasts and recent advances in the development of genetic Engineering tools in oleaginous yeasts within the last 3 years
Hyun Uk Kim - One of the best experts on this subject based on the ideXlab platform.
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toward systems Metabolic Engineering of streptomycetes for secondary metabolites production
Biotechnology Journal, 2018Co-Authors: Helene Lunde Robertsen, Tilmann Weber, Hyun Uk Kim, Sang Yup LeeAbstract:Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical trials in the last decades. A paradigm shift took place when the first whole genome sequences of streptomycetes became available, from which silent or "cryptic" biosynthetic gene clusters (BGCs) were discovered. Cryptic BGCs reveal a so far untapped potential of the microorganisms for the production of novel compounds, which has spurred new efforts in understanding the complex regulation between primary and secondary metabolism. This new trend has been accompanied with development of new computational resources (genome and compound mining tools), generation of various high-quality omics data, establishment of molecular tools, and other strain Engineering strategies. They all come together to enable systems Metabolic Engineering of streptomycetes, allowing more systematic and efficient strain development. In this review, the authors present recent progresses within systems Metabolic Engineering of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites.
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Metabolic Engineering of corynebacterium glutamicum for l arginine production
Nature Communications, 2014Co-Authors: Seok Hyun Park, Hyun Uk Kim, Tae Yong Kim, Jun Seok Park, Suoksu Kim, Sang Yup LeeAbstract:The amino acid, L-arginine, has important applications in the food, pharmaceutical and cosmetics industries. Here the authors systematically engineer a Corynebacterium glutamicum strain for the production of L-arginine, and show that their Metabolic Engineering approach can be used for the industrial production of valuable chemicals.
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Metabolic flux analysis and Metabolic Engineering of microorganisms
Molecular bioSystems, 2007Co-Authors: Hyun Uk Kim, Tae Yong Kim, Sang Yup LeeAbstract:Recent advances in Metabolic flux analysis including genome-scale constraints-based flux analysis and its applications in Metabolic Engineering are reviewed. Various computational aspects of constraints-based flux analysis including genome-scale stoichiometric models, additional constraints used for the improved accuracy, and several algorithms for identifying the target genes to be manipulated are described. Also, some of the successful applications of Metabolic flux analysis in Metabolic Engineering are reviewed. Finally, we discuss the limitations that need to be overcome to make the results of genome-scale flux analysis more realistically represent the real cell metabolism.
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systems Metabolic Engineering of escherichia coli for l threonine production
Molecular Systems Biology, 2007Co-Authors: Kwang Ho Lee, Tae Yong Kim, Hyun Uk Kim, Jin Hwan Park, Sang Yup LeeAbstract:Amino-acid producers have traditionally been developed by repeated random mutagenesis owing to the difficulty in rationally Engineering the complex and highly regulated Metabolic network. Here, we report the development of the genetically defined L-threonine overproducing Escherichia coli strain by systems Metabolic Engineering. Feedback inhibitions of aspartokinase I and III (encoded by thrA and lysC, respectively) and transcriptional attenuation regulations (located in thrL) were removed. Pathways for Thr degradation were removed by deleting tdh and mutating ilvA. The metA and lysA genes were deleted to make more precursors available for Thr biosynthesis. Further target genes to be engineered were identified by transcriptome profiling combined with in silico flux response analysis, and their expression levels were manipulated accordingly. The final engineered E. coli strain was able to produce Thr with a high yield of 0.393 g per gram of glucose, and 82.4 g/l Thr by fed-batch culture. The systems Metabolic Engineering strategy reported here may be broadly employed for developing genetically defined organisms for the efficient production of various bioproducts.