SHORTENING an industry’s supply chain is bound to affect the activities of its suppliers. That is as true of the recreational-drugs business as it is of any other. Some street pharmaceuticals, such as methamphetamine and cannabis, are already produced near their main consumer markets—whether cooked up in laboratories or grown under cover. But others, particularly cocaine and heroin, still have to be imported from far-flung places where the plants which produce them flourish in the open (think of poppies in Afghanistan).

If these internationally traded commodities could be produced locally, the cartels that now smuggle them might find themselves out of business. Astute drug barons will therefore be reading their copies of Nature Chemical Biology with particular interest—for the current edition of the journal contains a paper describing a technology that could completely disrupt their business.

It may, to be fair, also change the businesses of legitimate drug firms, because the authors of this paper, John Dueber of the University of California, Berkeley and his colleagues, have found the last pieces of a jigsaw puzzle that will permit opiates to be made from glucose through the agency of yeast. They have still to fit them with the other pieces, to form a single picture. But when they do so, which is likely to be soon, instead of fermenting sugar into alcohol, you will be able to ferment it into morphine—and into many other pharmacologically active molecules as well.

The path from glucose, biochemistry’s common currency, to morphine is a long one. The poppies that produce the stuff naturally go to the trouble because it confuses the nervous systems of potential pests. The synthesis has 15 steps, each requiring a particular enzyme.

Several groups of researchers have replicated its later stages in yeast, by borrowing appropriate enzymes (or, rather, the genetic material that encodes them) from poppies, and also from bacteria. These investigators have not, however, been able to backtrack in yeast beyond a molecule called S-reticuline, which is the hub of the process, in that it can act as the precursor for many morphine-like substances. They have managed to do this backtracking in E. coli—but that is a bacterium and thus works very differently from yeast, which is a fungus.

Strange brew
 
Dr Dueber and his team found the missing part of the puzzle in the genome of sugar beet. The crucial step leading to S-reticuline that previous workers had been unable to engineer into yeast is the transformation of a molecule called tyrosine into one called L-DOPA (itself a useful drug for the treatment of Parkinson’s disease). They needed a way to follow this reaction, in order to see if candidate enzymes they were testing actually worked. They found the answer in a substance that turns L-DOPA into a fluorescent yellow molecule. With this marker to hand, they were able to stick candidate enzyme after candidate enzyme into yeast DNA until they found one which made L-DOPA in reasonable quantities.

Having identified their target, the researchers set about improving it by a process of mutation and selection that mimics natural evolution. The upshot is a strain of yeast which makes S-reticuline from tyrosine, to go with the existing one that makes S-reticuline into morphine—and, since tyrosine is one of the 20 amino acids used to make proteins, yeast cells turn it out naturally from glucose. Once the two halves of the pathway, from tyrosine to S-reticuline, and from S-reticuline to morphine, are connected together in an appropriately engineered yeast cell, that cell will be able to make morphine from sugar.

Whether this will be better, from the point of view of legitimate drug companies, than extracting it from poppy sap, remains to be seen. But it looks promising. Moreover, it should be easy to attach the S-reticuline pathway to others than that leading to morphine, to make codeine, hydrocodone, hydromorphone and oxycodone, all of which are valuable painkillers; sanguinarine and berberine, which are antibiotics; and tubocurarine and papaverine, which are muscle relaxants.

Drug-smuggling syndicates, though, should be quaking in their boots. If strains of yeast that can turn out opiates are liberated from laboratories and pass into general circulation, brewing morphine-containing liquor for recreational use will be easy. It will be illegal, of course. And the authorities will, no doubt, try to crack down on it. But those who smuggle the stuff from places like Afghanistan may find themselves driven out of business by home-brew opium clubs based in garajes.