19 May 2015

New yeast Strain Synthesizes Opiate Precursor

Biotechnologists have created yeast that produces "blanks" of opiates

RIA News

Geneticists have developed a new variety of genetically modified yeast that converts sugar not into alcohol or carbon dioxide, but into raw materials for the manufacture of opiates and a number of drugs, according to an article published in the journal Nature Chemical Biology (DeLoache et al., An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose – VM).

"What we really want to do is feed glucose to yeast and teach it to perform all the chemical steps necessary to produce the molecules of the medicine that you need. In our study, we described each of these steps, and now it remains only to link them together and bring them to the industrial level. It's difficult, but feasible," says John Dueber from Concordia University in Quebec (Canada).

Duber and several other bioengineers have taken a potentially dangerous step towards synthetic opiates, trying to reproduce inside yeast the work of the most complex part of the enzyme chain that is responsible for the production of morphine and other opiates in poppy cells.

This part of the "conveyor" is responsible for the assembly of molecules of the so-called benzyl-iso–quinolines (BIH) - complex organic molecules from three hydrocarbon rings that form the basis of morphine, codeine, a number of other opiates, as well as several dozen anticancer and anticonvulsive drugs that can be found inside poppy seeds.

Similar molecules are glued together in maca cells from two molecules of the amino acid tyrosine, which are oxidized and changed in a special way before joining. Reproduction of this phase caused great difficulties for biochemists, since yeast cells lack the necessary details of this "conveyor".

Dubert's group solved this problem by inserting into the yeast genome the gene of another plant – ordinary beetroot, which allowed yeast to convert tyrosine into dopamine, a pleasure hormone and one of the "halves" of BIH molecules.


On the left – a common yeast culture, on the right – a transgenic strain,
synthesizing "blanks" of opiates. A snapshot from the UC Berkeley press release
Discovery paves way for homebrewed drugs, prompts call for regulation – VM.

This technique allowed scientists to reproduce about half of the links in the chain responsible for the production of morphine and other opiates. Considering that other parts of this pipeline were reproduced back in 2008 and 2011, biotechnologists now have the opportunity to grow full-fledged opium yeast by combining these developments. (In 2014, bioengineers from Stanford developed a method for producing opioid analgesics using GM yeast from one of the toxic alkaloids of poppy, thebaine – VM.)

"In principle, anyone with access to such a yeast variety and having basic skills in their fermentation will be able to grow a morphine–producing fungus using a conventional home brewing kit," warns Tanya Bubela from the University of Alberta in Edmonton (Canada), a biotechnological expert, not related with the authors of the article.

According to her, for this reason, all such studies should be conducted under the supervision of drug treatment services, and access to their findings, as well as to the yeast samples themselves, should be strictly limited. According to the expert, if such yeast falls into the hands of drug cartels in Mexico or in other disadvantaged countries, it will be almost impossible to suppress the production of such opiates.

The simplest method of solving this problem is to embed in yeast such gene chains that will make the fungus dependent on a number of synthetic substances, without which it will not be able to live outside the walls of the laboratory. In addition, special tags can be embedded in them that would help law enforcement agencies find cultures of opiate yeast using simple tests.

The authors of the article themselves urge to see the positive sides in their research – according to them, BIH and their derivatives can be used not only for the production of opiates, but also to create analogues of 2.5 thousand non-addictive molecules contained in poppy seeds and whose properties have not yet been studied.

Portal "Eternal youth" http://vechnayamolodost.ru19.05.2015

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