Aug
15
Genetic Engineering Runs High Speed Metabolism In Reverse
August 15, 2011 | 1 Comment
They must have some interesting brains storming sessions at Rice University. Bioengineering researchers at Rice have unveiled a new method for rapidly converting simple glucose, sugar, into biofuels and petrochemical substitutes. Rice’s team describes with a paper published online in Nature, how it reversed one of the most efficient of all metabolic pathways — the beta oxidation cycle — to engineer bacteria that produce biofuel at a much faster rate.
Beta oxidation is one of biology’s most fundamental processes. Species that use it range from single-celled bacteria to human beings. Beta oxidation breaks down fatty acids and generates energy.
In the research for the Nature study, Professor Gonzalez and students Clementina Dellomonaco, James Clomburg and Elliot Miller took a completely different approach by reversing the beta oxidation cycle by selectively manipulating about a dozen genes in the bacteria Escherichia coli. They also showed that selective manipulations of particular genes could be used to produce fatty acids of particular lengths, including long-chain molecules like stearic acid and palmitic acid, which have chains of more than a dozen carbon atoms.
“Rather than going with the process nature uses to build fatty acids, we reversed the process that it uses to break them apart,” Ramon Gonzalez, associate professor of chemical and biomolecular engineering at Rice and lead co-author of the Nature study said. “It’s definitely unconventional, but it makes sense because the routes nature has selected to build fatty acids are very inefficient compared with the reversal of the route it uses to break them apart.”
Just how quick is this breakthrough? On a cell-per-cell basis, the bacteria produced the butanol, the biofuel that can be substituted for gasoline in most engines, about 10 times faster than any previously reported organism.
Gonzalez, in discussing the basic test said, “That’s really not even a fair comparison because the other organisms used an expensive, enriched feedstock, and we used the cheapest thing you can imagine, just glucose and mineral salts.”
Butanol is, for the most part, a drop in biofuel source for gasoline. The production of butanol has been hampered due to the nature of butanol – it doesn’t mix with water like ethanol, and as concentration increases during production it tends to stop or kill the producing organism. But the increased energy over ethanol and the friendliness to mix with petroleum based gasoline makes butanol the big gasoline replacement goal.
Gonzales said, “We call these ‘drop-in’ fuels and chemicals, because their structure and properties are very similar, sometimes identical, to petroleum-based products. That means they can be ‘dropped in,’ or substituted, for products that are produced today by the petrochemical industry.”
Butanol is a relatively short molecule, with a backbone of just four carbon atoms. Molecules with longer carbon chains have been even more troublesome for biotech producers to make, particularly molecules with chains of 10 or more carbon atoms. Gonzalez said that’s partly because researchers have focused on ramping up the natural metabolic processes that cells use to build long-chain fatty acids.
Just how far can the study into commercialization and scale go? “This is not a one-trick pony,” Gonzalez said. “We can make many kinds of specialized molecules for many different markets. We can also do this in any organism. Some producers prefer to use industrial organisms other than E. coli, like algae or yeast. That’s another advantage of using reverse-beta oxidation, because the pathway is present in almost every organism.”
Gonzalez’s laboratory is racing with hundreds of labs around the world to find biomass sourced methods for producing chemicals like butanol that have historically come from petroleum.
Lots of questions are yet to be answered. For example, yeast-making ethanol goes a very good job of getting virtually all the starches and sugars made into fuel. Just how well the reversed process might work is yet to be explored. Ethanol separation is simple distillation; just how a reversed butanol process works isn’t explored.
But speed matters. Also the potential across organisms may well offer many more crop forms, perhaps cellulosic sources as well. The Rice team has started a new field for exploration and research.
The key is the striking and impressive innovation in choosing the research field. You don’t see “reversals’ often in research development, let alone applied to the genetic engineering. Rice and Gonzales with the team members have made an important contribution in progress both in the research of the organism, but the precepts used in thought to choose a research path.
It’s double the congratulations!
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