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Science  04 Aug 2006:
Vol. 313, Issue 5787, pp. 593
DOI: 10.1126/science.313.5787.593b

Superficially, biosynthetic pathways for natural products might be likened to factory assembly lines where having more workers would mean being able to make more product. When the costs of factory buildings, workers, and excess inventory of parts are factored in, a just-in-time process is a more efficient solution, so that workers are neither overburdened nor idle and no partially assembled products accumulate. Add in the biological complications of multiple assembly teams using some of the same parts along with feedback, feed-forward, and interpathway interactions, and calculating the optimal numbers of workers seems out of reach.

Pfleger et al. have instead developed an approach for constructing a library of artificial operons, which in this instance code for a three-enzyme segment of the isoprenoid pathway. By inserting into the intergenic regions variations of posttranscriptional regulatory elements, such as hairpin-forming sequences and ribonuclease sites (and perhaps riboswitches, too), they generate lots of combinations and find that increasing the hairpin-forming propensity of the ribosome binding site in front of the second gene is sufficient to reduce the mRNA levels of the second and third genes, which keeps acetyl CoA concentrations high enough to support vigorous growth and isoprenoid production simultaneously. — GJC

Nat. Biotechnol. 24, 10.1038/nbt1226 (2006).

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