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US researchers engineer cells for more efficient biofuel production

MIT team’s work to dramatically boost isobutanol production in yeast opens up opportunities for biochemicals

Work at the MIT to engineer cells is set to increase efficiency of biofuel production

Chemical engineers at the Massachusetts Institute of Technology (MIT) have engineered cells to increase efficiency of biofuel production. The US team has devised a way to dramatically boost isobutanol production in yeast. This involves engineering yeast so that isobutanol synthesis takes place entirely within mitochondria, cell structures that generate energy and also host many biosynthetic pathways. Using this approach, they were able to boost isobutanol production by around 260 per cent.

Though still short of the scale needed for industrial production, the advance suggests that this is a promising approach to engineering not only isobutanol but other useful chemicals as well, said Gregory Stephanopoulos, an MIT professor of chemical engineering.

“It’s not specific to isobutanol,” Stephanopoulos said. “It’s opening up the opportunity to make a lot of biochemicals inside an organelle that may be much better suited for this purpose compared to the cytosol of the yeast cells.”

Stephanopoulos collaborated with Gerald Fink, an MIT professor of biology and member of the Whitehead Institute, on this research. The lead author of the paper is Jose Avalos, a postdoc at the Whitehead Institute and MIT.

Historically, researchers have tried to decrease isobutanol production in yeast, because it can ruin the flavor of wine and beer. However, “now there’s been a push to try to make it for fuel and other chemical purposes,” said Avalos.

Yeast typically produce isobutanol in a series of reactions that take place in two different cell locations. The synthesis begins with pyruvate, a plentiful molecule generated by the breakdown of sugars such as glucose. Pyruvate is transported into the mitochondria, where it can enter many different metabolic pathways, including one that results in production of valine, an amino acid. 

The MIT researchers engineering the metabolic pathway’s enzymes to express a tag normally found on a mitochondrial protein, directing the cell to send them into the mitochondria.

This enzyme relocation boosted the production of isobutanol by 260 per cent, and yields of two related alcohols, isopentanol and 2-methyl-1-butanol, increased even more — 370 and 500 percent, respectively.

There are likely several explanations for the dramatic increase, the researchers say. One strong possibility, though difficult to prove experimentally, is that clustering the enzymes together makes it more likely that the reactions will occur, Avalos said.

The findings could have many applications in metabolic engineering. There are many situations where it could be advantageous to confine all of the steps of a reaction in a small space, which may not only boost efficiency but also prevent harmful intermediates from drifting away and damaging the cell.

“So far, they have done a good job showing that this idea works,” said James Liao, a professor of chemical and biomolecular engineering at UCLA, who was not part of the research team. “The next step is to see if this trend continues at a large scale and produces a high enough yield for commercial use.”

The research was funded by the National Institutes of Health and Shell Global Solutions.