Redox biocatalysis and metabolism: molecular mechanisms and metabolic network analysis.
Whole-cell biocatalysis utilizes native or recombinant enzymes produced by cellular metabolism to perform synthetically interesting reactions. Besides hydrolases, oxidoreductases represent the most applied enzyme class in industry. Oxidoreductases are attributed a high future potential, especially for applications in the chemical and pharmaceutical industries, as they enable highly interesting chemistry (e.g., the selective oxyfunctionalization of unactivated C-H bonds). Redox reactions are characterized by electron transfer steps that often depend on redox cofactors as additional substrates. Their regeneration typically is accomplished via the metabolism of whole-cell catalysts. Traditionally, studies towards productive redox biocatalysis focused on the biocatalytic enzyme, its activity, selectivity, and specificity, and several successful examples of such processes are running commercially. However, redox cofactor regeneration by host metabolism was hardly considered for the optimization of biocatalytic rate, yield, and/or titer. This article reviews molecular mechanisms of oxidoreductases with synthetic potential and the host redox metabolism that fuels biocatalytic reactions with redox equivalents. The tools discussed in this review for investigating redox metabolism provide the basis for studies aiming at a deeper understanding of the interplay between synthetically active enzymes and metabolic networks. The ultimate goal of rational whole-cell biocatalyst engineering and use for fine chemical production is discussed.
Blank
Lars M
LM
TU Dortmund, Germany. lars.blank@bci.tu-dortmund.de <lars.blank@bci.tu-dortmund.de>
Ebert
Birgitta E
BE
Buehler
Katja
K
Bühler
Bruno
B
D000818:Animals; D055162:Biocatalysis; D004734:Energy Metabolism; D053858:Metabolic Networks and Pathways; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D013379:Substrate Specificity
D010088:Oxidoreductases; D010544:Peroxidases; D010105:Oxygenases