Posted on 11/29/2022 12:39:49 PM PST by Red Badger
Used by humans as a stimulant and anesthetic for thousands of years, the drug commonly known as cocaine has been carefully shaped by species of the coca plant (Erythroxylum) over tens of millions of years in an arms race against hungry insects.
Knowing just how the plants pull off this feat of chemical engineering would be a big win for the pharmaceutical industry while helping biologists better understand the evolution of similar pesticides across the plant kingdom.
Yet the sheer complexity of the chemical's production has been one of nature's best-kept secrets, one that scientists have spent the better part of a century untangling.
Now, researchers from China's Kunming Institute of Botany have finally uncovered the last major steps of the biosynthetic process.
Not only did they more or less map the biochemical pathway of cocaine's production, but the researchers also reconstructed the entire chain inside a humble tobacco plant for good measure.
The process of forcing tobacco to churn out cocaine is unlikely to ever improve on current methods of production, nor provide any serious advances on new ways to spin out stimulants.
But a similar method involving bacteria or yeast could one day revolutionize the way we design and industrialize pharmaceuticals.
Cocaine is a member of a class of organic molecules known as tropane alkaloids. A whole family of plants evolved ways of making these chemicals to thwart herbivores, and in turn, we humans have taken advantage of the incidental effects they have on our own biology.
Hyoscyamine, for instance, is a tropane alkaloid. Made by deadly nightshade (Atropa belladonna), we've used hyoscyamine medicinally to dilate our pupils, paralyze our spit glands during surgery, and treat our fluttering hearts for more than a century.
The history of cocaine use could be a longer one, from chewing coca leaves for an energy boost since ancient times to using it as a topical anesthetic in modern surgery to its psychoactive effects in the form of an illicit recreational drug.
Chemically speaking, cocaine has a lot in common with hyoscyamine, with a recent discovery that both emerge from the same precursor – a molecule called 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid (or MPOA for short).
The structural difference between the two molecules is subtle but critical, though just how Erythroxylum mitigates the crucial transformation from MPOA to cocaine has until now remained a mystery.
Fortunately, the small contrast in molecular structures was enough for researchers to confine their search to a particular group of proteins, leading to the discovery of a pair of enzymes dubbed EnCYP81AN15 and EnMT4.
The molecular origami each is responsible for not only fills in crucial steps on how cocaine arises out of a convoluted chemical production line but reinforces the relationship between two pharmacologically significant plant compounds.
There remain a few small holes in the map, though researchers are confident enzymes well known to biochemistry could easily do the job.
To demonstrate this, they plugged six cocaine-production genes into the tobacco plant, Nicotiana benthamiana, leaving the genetic hybrid to fill in the gaps using its own versions of the suspected enzymes.
Sure enough, the engineered tobacco plants generated cocaine, providing rough proof that the team had a working knowledge of how cocaine is made.
Putting aside questions of how it might impact its illicit manufacture – if at all – the knowledge could have profound implications for the pharmaceutical industry, allowing researchers to tweak the formula and potentially uncover new bioactive compounds with far more efficiency.
Derivatives of cocaine, such as cocaine hydrochloride, have been approved for use by the FDA as local anesthetics as recently as 2020, demonstrating this age-old stimulant is far from a relic of history.
This research was published in Journal of the American Chemical Society.
This would have been a brilliant move until some numb nut spilled the beans
Smo-Caine
ISWYDT........................
China unseating Latin America as the chief cocaine producer, without the need for coca-friendly environment? The ramifications are astounding. Of course they would have to keep the Frankencoca plants from being grabbed up by the cartels, who recently successfully financed a genetically-modified hardy coca plant, Boliviana negra.
Coming soon to a 7-Eleven near you... “Marlboro White” with an extra special buzz.
(Actually I don’t think that would work, as it’s my understanding that cocaine decomposes when burned. That’s why Hunter Biden et al. have to first convert it into crack before it can be smoked)
Perhaps this has more a future in the chewing tobacco industry. Considering all the baseball players/managers over the years who’ve had an affinity for both chew and coke, this could offer a two-fer. Paging Ron Washington...
The cartels will be planting it if it is easier and cheaper to grow and process. I suspect it is more finicky than coca bushes.
That would explain why Cuban cigars are so good....
Cainbacco
If you thought quitting smoking was tough before....
That’s some trick. It took Coca-Cola 26 years to figure out how to grow coca plants with no cocaine in the leaves.
Everybody knows Coke (soft drink) originally contained cocaine. In 1903 they decided to yield to public pressure to remove it but the ingredients patent they made Coca-Cola under required that it contain coca leaves. So they initially used “spent” leaves that were mostly cocaine-free but it still contained trace amounts. You’d die from diabetes before you could drink enough of the new formula to got high on it, but there still was a ‘trace’ amount of cocaine in Coca-Cola.
Until 1929. By then they’d figured out how to grow cocaine-free coca.
Which sounds to me like decaffeinated coffee. Or alcohol-free beer. I hardly see the point.
LOL
tax dollars at work...
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