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      Advances in metabolic engineering of Corynebacterium glutamicum to produce high-value active ingredients for food, feed, human health, and well-being

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          Abstract

          The soil microbe Corynebacterium glutamicum is a leading workhorse in industrial biotechnology and has become famous for its power to synthetise amino acids and a range of bulk chemicals at high titre and yield. The product portfolio of the microbe is continuously expanding. Moreover, metabolically engineered strains of C. glutamicum produce more than 30 high value active ingredients, including signature molecules of raspberry, savoury, and orange flavours, sun blockers, anti-ageing sugars, and polymers for regenerative medicine. Herein, we highlight recent advances in engineering of the microbe into novel cell factories that overproduce these precious molecules from pioneering proofs-of-concept up to industrial productivity.

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          Plant polyphenols as dietary antioxidants in human health and disease

          Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.
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            From zero to hero--design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production.

            Here, we describe the development of a genetically defined strain of l-lysine hyperproducing Corynebacterium glutamicum by systems metabolic engineering of the wild type. Implementation of only 12 defined genome-based changes in genes encoding central metabolic enzymes redirected major carbon fluxes as desired towards the optimal pathway usage predicted by in silico modeling. The final engineered C. glutamicum strain was able to produce lysine with a high yield of 0.55 g per gram of glucose, a titer of 120 g L(-1) lysine and a productivity of 4.0 g L(-1) h(-1) in fed-batch culture. The specific glucose uptake rate of the wild type could be completely maintained during the engineering process, providing a highly viable producer. For these key criteria, the genetically defined strain created in this study lies at the maximum limit of classically derived producers developed over the last fifty years. This is the first report of a rationally derived lysine production strain that may be competitive with industrial applications. The design-based strategy for metabolic engineering reported here could serve as general concept for the rational development of microorganisms as efficient cellular factories for bio-production. Copyright © 2011 Elsevier Inc. All rights reserved.
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              A field of dreams: Lignin valorization into chemicals, materials, fuels, and health-care products

              Lignin is one of the most abundant renewable resources on earth and is readily produced as a sidestream during biomass fractioning. So far, these large quantities of lignin have been severely underutilized, thereby wasting this valuable renewable. Recent technological advances in lignin recovery, breakdown, and conversion have now started forming the first sustainable value chains to take advantage of lignin. Microbial cell factories, inspired by nature's miscellaneous set of lignin-degrading microbes, are at the heart of these novel processes. Recent success stories in which the enzymes and pathways of these microbes were harnessed for biobased production from lignin hold great promise for a sustainable upgrading of this renewable polymer into value-added compounds.
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                Author and article information

                Contributors
                Journal
                Essays Biochem
                Essays Biochem
                ebc
                Essays in Biochemistry
                Portland Press Ltd.
                0071-1365
                1744-1358
                July 2021
                26 July 2021
                : 65
                : 2 , Microbial Cell Factories
                : 197-212
                Affiliations
                [1 ]Institute of Systems Biotechnology, Saarland University, Saarbrücken, Germany
                [2 ]Institute for Frontier Science Initiative, Kanazawa University, Japan
                [3 ]Graduate School of Science, Technology and Innovation, Kobe University, Japan
                [4 ]Graduate School of Engineering, Kobe University, Japan
                [5 ]Biomass Engineering Research Division, RIKEN, Yokohama, Japan
                [6 ]Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, Germany
                [7 ]Institute of Biotechnology, RWTH Aachen University, Aachen, Germany
                [8 ]The Bioeconomy Science Center (BioSC), Forschungszentrum Jülich, Germany
                [9 ]Genetics of Prokaryotes, Biology & CeBiTec, Bielefeld University, Germany
                Author notes
                Correspondence: Christoph Wittmann ( christoph.wittmann@ 123456uni-saarland.de )
                Author information
                http://orcid.org/0000-0003-3473-0012
                http://orcid.org/0000-0002-7952-985X
                Article
                EBC20200134
                10.1042/EBC20200134
                8313993
                34096577
                af73729e-c79f-4751-a7b2-32d5e65b0947
                © 2021 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 14 March 2021
                : 26 April 2021
                : 27 April 2021
                Page count
                Pages: 16
                Categories
                Biotechnology
                Microbiology
                Synthetic Biology
                Review Articles

                corynebacterium glutamicum,extremolytes,metabolic engineering,plant phenols,synthetic biology,terpenoids

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