4 ms·

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 thebai

by leoh 11y ago

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 http://www.genome.jp/dbget-bin/www_bget?cpd:C06173.

dekhn 11y ago
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 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.

by leoh 11y ago

dekhn 11y ago

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 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.