caa a22 4500 606212523 CHVBK 20210128101043.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s10295-014-1560-y doi (NATIONALLICENCE)springer-10.1007/s10295-014-1560-y Metabolic engineering of carbon and redox flow in the production of small organic acids [Elektronische Daten] [Chandresh Thakker, Irene Martínez, Wei Li, Ka-Yiu San, George Bennett] The review describes efforts toward metabolic engineering of production of organic acids. One aspect of the strategy involves the generation of an appropriate amount and type of reduced cofactor needed for the designed pathway. The ability to capture reducing power in the proper form, NADH or NADPH for the biosynthetic reactions leading to the organic acid, requires specific attention in designing the host and also depends on the feedstock used and cell energetic requirements for efficient metabolism during production. Recent work on the formation and commercial uses of a number of small mono- and diacids is discussed with redox differences, major biosynthetic precursors and engineering strategies outlined. Specific attention is given to those acids that are used in balancing cell redox or providing reduction equivalents for the cell, such as formate, which can be used in conjunction with metabolic engineering of other products to improve yields. Since a number of widely studied acids derived from oxaloacetate as an important precursor, several of these acids are covered with the general strategies and particular components summarized, including succinate, fumarate and malate. Since malate and fumarate are less reduced than succinate, the availability of reduction equivalents and level of aerobiosis are important parameters in optimizing production of these compounds in various hosts. Several other more oxidized acids are also discussed as in some cases, they may be desired products or their formation is minimized to afford higher yields of more reduced products. The placement and connections among acids in the typical central metabolic network are presented along with the use of a number of specific non-native enzymes to enhance routes to high production, where available alternative pathways and strategies are discussed. While many organic acids are derived from a few precursors within central metabolism, each organic acid has its own special requirements for high production and best compatibility with host physiology. Society for Industrial Microbiology and Biotechnology, 2014 Oxidation-reduction nationallicence Redox nationallicence Succinate nationallicence Fatty acid nationallicence Formate nationallicence Propionate nationallicence Gene nationallicence Mutation nationallicence Metabolism nationallicence Pathway nationallicence Microbe nationallicence Thakker Chandresh Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA aut Martínez Irene Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Av. Brasil 2085, Casilla 4059, Valparaíso, Chile aut Li Wei Department of Bioengineering, Rice University, Houston, TX, USA aut San Ka-Yiu Department of Bioengineering, Rice University, Houston, TX, USA aut Bennett George Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA aut Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/3(2015-03-01), 403-422 1367-5435 42:3<403 2015 42 10295 https://doi.org/10.1007/s10295-014-1560-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10295-014-1560-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Thakker Chandresh Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA aut NATIONALLICENCE 700 1- Martínez Irene Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Av. Brasil 2085, Casilla 4059, Valparaíso, Chile aut NATIONALLICENCE 700 1- Li Wei Department of Bioengineering, Rice University, Houston, TX, USA aut NATIONALLICENCE 700 1- San Ka-Yiu Department of Bioengineering, Rice University, Houston, TX, USA aut NATIONALLICENCE 700 1- Bennett George Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA aut NATIONALLICENCE 773 0- Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/3(2015-03-01), 403-422 1367-5435 42:3<403 2015 42 10295