High yield biofuels production using engineered "non-fermentative" pathways in microbes.

A paper in last week's Nature demonstrated a combination of genetic modifications that allowed E. coli to produce isobutanol from glucose at 86% of the theoretical maximum yield.  Please people, slow down!  How am I supposed to finish writing my book if you keep innovating at this rate?

I jest, of course.  Mostly.

Atsumi, et al., exploit non-fermentative synthesis to maximize the production of molecules that could be used as biofuels, while minimizing parasitic side reactions that serve to "distract" their microbial work horse (here is the abstract in Nature).  The authors deleted 7 native genes, added several more from yeast and other microbes, and also added a plasmid containing what looks like another 6 or so genes and regulatory elements.  The plasmid was used to overexpress genes in a native E. coli synthesis pathway.  So call it ~15 total changes.

While the various genetic changes were made using traditional cloning techniques, rather than by synthesis, I would still put this project squarely in the category of synthetic biology.  True, there is no evident quantitative modeling, but it is still a great story.  I am impressed by the flavor of the article, which makes it sound like the project was cooked up by staring at a map of biochemical process (here is a good one at ExPASy -- you can click on the map for expanded views) and saying, "Hmmm... if we rewired this bit over here, and deleted that bit over there, and then brought in another bit from this other bug, then we might have something."  Molecular Legos, in other words.

As far as utility in the economy goes, the general method of engineering a biosynthesis pathway to produce fuels appears has, according to the press release from UCLA, been licensed to Gevo.  Gevo was founded by Francis Arnold, Matthew Peters, and Peter Meinhold of the California Institute of Technology and was originally funded by Vinod Khosla.

It is not clear how much of the new technology can be successfully claimed in a patent.  Dupont a published application from last spring (Update -- typed too fast)  Dupont had an application published last spring that claims bugs engineered to produce fuels via the Ehrlich pathway, and it appears to be very similar to what is in the Atsumi paper described above.  Here is the DuPont application at the USPTO, oddly entitled "Fermentive production of four carbon alcohols".  The "four-carbon" bit might be the out for the UCLA team and Gevo, as they demonstrate ways to build molecules with four and more carbons.  Time, and litigation, will tell who has the better claims.  And then both groups probably have to worry about patents held by Amyris, which is probably also claiming the use of engineered metabolic synthesis for biofuels.  Ah, the joys of highly competitive capitalism.  But, really, it is all good news because all the parties above are trying to move rapidly beyond ethanol.

I am no fan of ethanol as a biofuel, as it has substantially lower energy density than gasoline and soaks up water even better than a sponge.  If ethanol were the only biofuel around, then I suppose we would have to settle for it despite the disadvantages.  But, obviously, new technologies are rapidly being demonstrated that produce other, better, biofuels.  The Atsumi paper serves as yet more evidence that biological technologies will prove a substantial resource in weaning ourselves from fossil fuels (see  my earlier posts "The Need for Fuels Produced Using Synthetic Biology" and "The Intersection of Biofuels and Synthetic Biology").