Metabolic engineering of carbon and redox flow in the production of small organic acids

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dc.citation.journalTitleJournal of Industrial Microbiology & Biotechnologyen_US
dc.contributor.authorThakker, Chandreshen_US
dc.contributor.authorMartínez, Ireneen_US
dc.contributor.authorLi, Weien_US
dc.contributor.authorSan, Ka-Yiuen_US
dc.contributor.authorBennett, George N.en_US
dc.date.accessioned2015-01-16T16:13:08Zen_US
dc.date.available2015-01-16T16:13:08Zen_US
dc.date.issued2014en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationThakker, Chandresh, Martínez, Irene, Li, Wei, et al.. "Metabolic engineering of carbon and redox flow in the production of small organic acids." <i>Journal of Industrial Microbiology & Biotechnology,</i> (2014) Springer: http://dx.doi.org/10.1007/s10295-014-1560-y.en_US
dc.identifier.doihttp://dx.doi.org/10.1007/s10295-014-1560-yen_US
dc.identifier.urihttps://hdl.handle.net/1911/78927en_US
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer.en_US
dc.subject.keywordoxidation-reductionen_US
dc.subject.keywordredoxen_US
dc.subject.keywordsuccinateen_US
dc.subject.keywordfatty aciden_US
dc.subject.keywordformateen_US
dc.subject.keywordpropionateen_US
dc.subject.keywordgeneen_US
dc.subject.keywordmutationen_US
dc.subject.keywordmetabolismen_US
dc.subject.keywordpathwayen_US
dc.subject.keywordmicrobeen_US
dc.titleMetabolic engineering of carbon and redox flow in the production of small organic acidsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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