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      Metabolic engineering of microorganisms for production of aromatic compounds

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          Abstract

          Metabolic engineering has been enabling development of high performance microbial strains for the efficient production of natural and non-natural compounds from renewable non-food biomass. Even though microbial production of various chemicals has successfully been conducted and commercialized, there are still numerous chemicals and materials that await their efficient bio-based production. Aromatic chemicals, which are typically derived from benzene, toluene and xylene in petroleum industry, have been used in large amounts in various industries. Over the last three decades, many metabolically engineered microorganisms have been developed for the bio-based production of aromatic chemicals, many of which are derived from aromatic amino acid pathways. This review highlights the latest metabolic engineering strategies and tools applied to the biosynthesis of aromatic chemicals, many derived from shikimate and aromatic amino acids, including l-phenylalanine, l-tyrosine and l-tryptophan. It is expected that more and more engineered microorganisms capable of efficiently producing aromatic chemicals will be developed toward their industrial-scale production from renewable biomass.

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          THE SHIKIMATE PATHWAY.

          The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.
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            A comprehensive metabolic map for production of bio-based chemicals

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              Assessment of Variability in the SOMAscan Assay

              SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity and specificity. In this work, we present a comprehensive meta-analysis of performance based on multiple serum and plasma runs using the current 1.3 k assay, as well as the previous 1.1 k version. We discuss normalization procedures and examine different strategies to minimize intra- and interplate nuisance effects. We implement a meta-analysis based on calibrator samples to characterize the coefficient of variation and signal-over-background intensity of each protein analyte. By incorporating coefficient of variation estimates into a theoretical model of statistical variability, we also provide a framework to enable rigorous statistical tests of significance in intervention studies and clinical trials, as well as quality control within and across laboratories. Furthermore, we investigate the stability of healthy subject baselines and determine the set of analytes that exhibit biologically stable baselines after technical variability is factored in. This work is accompanied by an interactive web-based tool, an initiative with the potential to become the cornerstone of a regularly updated, high quality repository with data sharing, reproducibility, and reusability as ultimate goals.
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                Author and article information

                Contributors
                +82-42-350-3930 , leesy@kaist.ac.kr
                Journal
                Microb Cell Fact
                Microb. Cell Fact
                Microbial Cell Factories
                BioMed Central (London )
                1475-2859
                26 February 2019
                26 February 2019
                2019
                : 18
                : 41
                Affiliations
                [1 ]ISNI 0000 0001 2292 0500, GRID grid.37172.30, Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program) and Institute for the BioCentury, , Korea Advanced Institute of Science and Technology (KAIST), ; Daejeon, 34141 Republic of Korea
                [2 ]ISNI 0000 0001 2292 0500, GRID grid.37172.30, Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, , KAIST, ; Daejeon, 34141 Republic of Korea
                [3 ]ISNI 0000 0001 2292 0500, GRID grid.37172.30, BioProcess Engineering Research Center and Bioinformatics Research Center, , KAIST, ; Daejeon, 34141 Republic of Korea
                Author information
                http://orcid.org/0000-0003-0599-3091
                Article
                1090
                10.1186/s12934-019-1090-4
                6390333
                30808357
                d00f4a70-c683-4e01-8fc3-23e6d9a26b65
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 January 2019
                : 19 February 2019
                Funding
                Funded by: Ministry of Science and ICT
                Award ID: 2011-0031963
                Award Recipient :
                Funded by: Ministry of Science and ICT
                Award ID: NRF-2012M1A2A2026556
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Biotechnology
                aromatic compounds,metabolic engineering,synthetic biology,shikimate pathway,phenylalanine,tyrosine,tryptophan

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