« More on Warp Drive Bio and Cryptic Natural Products |
| Exposing Faked Scientific Papers »
September 6, 2013
Making the Bacteria Make Your Fluorinated Compounds
Acetate is used in vivo as a starting material for all sorts of ridiculously complex natural products. So here's a neat idea: why not hijack those pathways with fluoroacetate and make fluorinated things that no one's ever seen before? That's the subject of this new paper in Science, from Michelle Chang's lab at Berkeley.
There's the complication that fluoroacetate is a well-known cellular poison, so this is going to be synthetic biology all the way. (It gets processed all the way to fluorocitrate, which is a tight enough inhibitor of aconitase to bring the whole citric acid cycle to a shuddering halt, and that's enough to do the same thing to you). There a Streptomyces species that has been found to use fluoroacetate without dying (just barely), but honestly, I think that's about it for organofluorine biology.
The paper represents a lot of painstaking work. Finding enzymes (and enzyme variants) that look like they can handle the fluorinated intermediates, expressing and purifying them, and getting them to work together ex vivo are all significant challenges. They eventually worked their way up to 6-deoxyerythronolide B synthase (DEBS), which is a natural goal since it's been the target of so much deliberate re-engineering over the years. And they've managed to produce compounds like the ones shown, which I hope are the tip of a larger fluorinated iceberg.
It turns out that you can even get away with doing this in living engineered bacteria, as long as you feed them fluoromalonate (a bit further down the chain) instead of fluoroacetate. This makes me wonder about other classes of natural products as well. Has anyone ever tried to see if terpenoids can be produced in this way? Some sort of fluorinated starting material in the mevalonate pathway, maybe? Very interesting stuff. . .
+ TrackBacks (0) | Category: Chemical Biology | Chemical News | Natural Products
POST A COMMENT
- RELATED ENTRIES
- Merck's Aftermath
- Models and Reality
- Rewriting History at the Smithsonian?
- The FDA: Too Loose, Or Appropriately Brave?
- More Magic Methyls, Please
- Totaling Up a Job Search
- Humble Enzyme Dodges Spotlight
- Unraveling An Off-Rate