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Re:Modified yeast produce opiates from sugar by dekhn on Friday August 14, 2015 @12:02PM (#10060869)
This is an absurd technical accomplishment. Identifying and cloning 21 genes on its own is a ton of work, but doing so in a way that replicates a synthetic pathway is amazing. Hats off to the scientists who managed to get this to work.
Re:Modified yeast produce opiates from sugar by dbbolton on Friday August 14, 2015 @07:00PM (#10063500)
Six or so years ago, a friend of mine and I were talking about how the US had destroyed poppy fields in Afghanistan on a large scale (I think to block Taliban funding or something) despite the WHO listing morphine as a critical drug in short supply.

Being enterprising sophomore Bio students who had a basic grasp on cellular machinery, we then somehow spun that story into the idea of mass-producing plant alkaloids from rapidly reproducing microbes (except we imagined bacteria rather than fungi). We always had "crazy" discussions like that and I never gave it a second thought afterward.

What's really funny to me is what a pipe dream (no pun intended) it seemed like at the time-- maybe the beginning of a bad sci-fi story at best. But here we are today and it's so incredible to me that this team was able to bring that idea to life.

Now I'm left wondering what other crazy discussions will turn into practical real-world applications in the next six years.

Re:Modified yeast produce opiates from sugar by dekhn on Friday August 14, 2015 @08:18PM (#10063763)
You're not the only person who has thought along those lines. I've seen multiple proposals to mass-produce plant alkaloids using microbes (bacteria or yeast). Very few people have the skills required to do this; you have to be an expert in chemistry, as well as molecular biology, and also be patient and good at running experiments and getting funded. And you've probably also have to be lucky in choosing what synthesis to work on.

This falls under the "Synthetic Biology" domain: https://en.wikipedia.org/wiki/Synthetic_biology is a decent introduction to the concepts.

See also the iGEM competition: https://www.igem.org/Main_Page the students who work on those projects often come up with really clever ideas and implementations, which has the potential to push the field along faster than if it was just academically funded professors and some startups.

Re:Modified yeast produce opiates from sugar by dbbolton on Friday August 14, 2015 @08:43PM (#10063833)
I'm well aware that ideas are a dime a dozen and that there is no realistic way that I could have brought that idea to life.

I wasn't trying to make a "I had that idea first! I could have made millions!" type of comment. My point was just how wild it is that it seemed to unrealistic at the time but now it's reality. I also thought it was an interesting coincidence that we happened to think of the same alkaloid that this project created.

Re:Modified yeast produce opiates from sugar by pixl97 on Friday August 14, 2015 @03:30PM (#10062324)
Once the proper genes to make this work are identified by one group, how hard is it for another group to replicate the results?

I'm just wondering when drugs are created with this method if bioengineers will be able to 'easily' create reproductions of the yeast by following a template of the process, or if people in their footsteps will be mostly using clones of their original work.

Re:Modified yeast produce opiates from sugar by dekhn on Friday August 14, 2015 @03:51PM (#10062494)
it's entirely non trivial. cloning genes is tedious, slow, manual labor. People are working on scaling it up (so more genes can be cloned at a time) and making it easier (so you can press a button and receive a yeast).

Rather than directly replicating the experiment, it would be easier for the team to disseminate their cells to others, who could then grow the cells up, sequence them, and compare the sequence to a wild type yeast to verify the genes were included, then do a few other transcription experiments and blocking assays to show that the genes that got cloned in were actually the ones carrying out the synthesis.

Re:Modified yeast produce opiates from sugar by leoh on Saturday August 15, 2015 @02:48AM (#10064570)
It is impressive. But I'm going to burst your bubble. The team did not necessarily discover an entirely new biosynthetic pathway. Endogenous pathways for thebaine/opiate synthesis have been known for some time; for example: http://www.genome.jp/dbget-bin/www_bget?cpd:C06173.
Re:Modified yeast produce opiates from sugar by dekhn on Saturday August 15, 2015 @12:55PM (#10065914)
Fair criticism. I didn't say that they discovered an entirely new biosynthetic pathway. I said they identified and cloned genes (I think your confusion stems from a false interpretation of what I said; I didn't mean to imply that the team identified every single gene). Those are two different things; note for example the link you pointed me at is effectively an abstract pathway.

So, since you're making a technical nitpick with a short detail of my comment, I'll apply the full flame of my technical capabilities. We'll start with the paper itself:

The abstract says " We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself"

So the authors say that they discovered enzymes. This is consistent with my statement. Your statement is irrelevant; discovering a biosynthetic pathway is a distinct thing from discovering the enzymes that carry it out (but, I will agree that in many cases, when you discover a biosynthetic pathway you can identify the enzymes and genes that code for them at the same time. It's not necessary, though). What the authors did here is engineer a biosynthetic pathway.

Next statment that supports my position from the paper: "Also, key enzyme(s) that epimerize the (S)-benzylisoquinoline scaffold to the (R)-enantiomer, which is the biosynthetic precursor of the promorphinan and morphinan scaffolds, have remained unknown even after decades of study until recently identified by two groups (19, 20) and by our team as described below."

Note the above extract from the paper, if correct, completely abolishes your point. The authors cite their own recent work, as well as the work of others, which was required for engineering biosynthetic pathway.

Here is a link to the author's prior work identifying a required step in the process: http://www.sciencemag.org/content/349/6245/309

At this point I rest my case. My original statement stands, as it does, and your criticism appears to be only a pointless and ultimately irrelevant nitpick of my statement.

Further, I would appreciate not using the term "burst your bubble". It's immature, and when said to a person who's been studying synthetic biology for more than 2 decades, who can read the primary literature, and compose a coherent reply, makes you look petty.

Re:Modified yeast produce opiates from sugar by david_b on Saturday August 15, 2015 @06:13AM (#10064952)
It's definitely very impressive - just five years ago they still had to feed the yeast precursors:

http://www.theglobeandmail.com/technology/science/canadian-s...