Homeostatic Engineering

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Science  16 Apr 2010:
Vol. 328, Issue 5976, pp. 286
DOI: 10.1126/science.328.5976.286-a

Not so many years ago, adding a heterologous set of enzymes in order to augment the biosynthetic capacity of a microbe was acknowledged as a remarkable feat of rational design. Apart from the important technical concerns of efficiency and stability, attention then turned to the greater challenge of repairing metabolic dysfunction; the goal here was not only to restore the biochemical reactions but also to place them under endogenous regulation. Kemmer et al. demonstrate how this might be achieved in mice suffering from excess uric acid, which in humans can lead to the condition commonly known as gout. Uric acid is the product of purine catabolism, and in mice, urate oxidase converts it to allantoin, which is excreted. Excess uric acid can precipitate as the sodium salt, and humans, who lack urate oxidase, cannot tolerate too much of it. Conversely, uric acid can scavenge free radicals, and a moderate amount is deemed to be beneficial. Stitching together a mini-circuit comprising a Deinococcus transcriptional repressor and promoter as well as Aspergillus urate oxidase enabled these authors to maintain serum uric acid concentration in urate oxidase–deficient mice at normal physiologic levels.

Nat. Biotechnol. 28, 10.1038/nbt.1617 (2010).

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