Tuesday, November 16, 2004

These poppies won't make you sleep

Scientists used RNA interference to knock out a gene in opium poppies, and got unexpected results.

They managed to turn off the second-to-last gene in a series of genes that lead to morphine. Surprisingly, they did not get an accumulation of the second-to-last intermediate product, but a product seven steps upstream. Somehow, the process piled up at that point, and didn't continue much past it, even though the machinery to carry it forward should still have been in working order.

The usual model, which works great in bacteria, is that the synthesis of a compound will go through a bunch of steps, A->B->C->D->...->Z.

Knocking out step Y should cause a build-up of the results from step X, and in bacteria that's what you get. In opium poppies, the result is a build-up of the results from the enzyme seven steps preceding X. (That would be step Q, for those who are counting.)

Now what?

Well, first of all, the result of this step is very useful in its own right, being a precursor for anticancer and anti-malarial drugs. Second, it gives researchers something to investigate. There are several reasons why the pile-up might have occurred just where it did:

Larkin and colleagues suggest the unexpected reticuline phenotype may have been caused by a buildup of morphine substrates codeinone and neopinione that triggered negative feedback on one or more earlier enzymes or transport steps of the morphine branch. Alternatively, the substrate feedback may have inhibited transcription of genes encoding earlier enzymes or transporters. Loss of COR enzyme from a larger interdependent enzyme complex may also have disabled the other enzyme reactions normally associated with the complex.

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