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jueves, 21 de mayo de 2015

Las levaduras pueden producir morfina y opiáceos

Biotechnology is about to make morphine production as simple as brewing beer. A paper published on 18 May in Nature Chemical Biology reports the creation of a yeast strain containing the first half of a biochemical pathway that turns simple sugars into morphine — mimicking the process by which poppies make opiates. Combined with other advances, researchers predict that it will be only a few years — or even months — before a single engineered yeast strain can complete the entire process.

Dueber and colleagues’ work does not reach that goal. But it demonstrates that, given the right genes and biochemical machinery, yeast can convert glucose into the intermediate compound (S)-reticuline — the first half of the poppy’s morphine-production pathway.

Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA intermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To aid in this effort, we developed an enzyme-coupled biosensor for the upstream intermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, we identified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8-fold via PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to our knowledge the first demonstration of dopamine production from glucose in yeast, with a 7.4-fold improvement in titer obtained for our best mutant enzyme. We extended this pathway to fully reconstitute the seven-enzyme pathway from L-tyrosine to (S)-reticuline. Future work to improve titers and connect these steps with downstream pathway branches, already demonstrated in S. cerevisiae, will enable low-cost production of many high-value BIAs.

Acceso al trabajo

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