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

  • Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

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.

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Acknowledgments

This work was supported by NSF CBET-1033552. I.M. acknowledges the financial support by FONDECYT 11110411.

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Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA

    Chandresh Thakker & George N. Bennett

  2. Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Av. Brasil 2085, Casilla 4059, Valparaíso, Chile

    Irene Martínez

  3. Department of Bioengineering, Rice University, Houston, TX, USA

    Wei Li & Ka-Yiu San

  4. Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA

    Ka-Yiu San

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  1. Chandresh Thakker
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  2. Irene Martínez
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  3. Wei Li
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  4. Ka-Yiu San
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  5. George N. Bennett
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Correspondence to George N. Bennett.

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Special Issue: Metabolic Engineering.

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Thakker, C., Martínez, I., Li, W. et al. Metabolic engineering of carbon and redox flow in the production of small organic acids. J Ind Microbiol Biotechnol 42, 403–422 (2015). https://doi.org/10.1007/s10295-014-1560-y

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