BY ROBERT F SERVICE
Synthetic biologists have performed a biochemical switcheroo. They’ve re-engineered a bacterium that normally eats a diet of simple sugars into one that builds its cells by absorbing carbon dioxide (CO2), much like plants. The work could lead to engineered microbes that suck CO2 out of the air and turn it into medicines and other high-value compounds.
“The implications of this are profound,” says Dave Savage, a biochemist at the University of California, Berkeley, who was not involved with the work. Such advances, he says, could “ultimately make us change the way we teach biochemistry.”
Biologists typically break the world up into two types of organisms: autotrophs and heterotrophs. The former, mainly plants and some bacteria, mostly use photosynthesis to convert CO2 into sugars and other organic compounds they need to build their cells. Most everything else, including us, gets those building blocks from the organisms they consume.
Synthetic biologists have long tried to engineer plants and autotrophic bacteria to produce valuable chemicals and fuels from water and CO2, because it has the potential to be cheaper than other routes. But so far they’ve been far more successful at getting the heterotrophic bacterium Escherichia coli—known to most people as the microbe that lives in our guts and sometimes triggers food poisoning—to produce ethanol and other desired chemicals more cheaply than other approaches. It’s not always cheap, however; these engineered E. coli strains must eat a steady diet of sugars, increasing the costs of the effort.
So, Ron Milo, a synthetic biologist at the Weizmann Institute of Science in Rehovot, Israel, and his colleagues decided to see whether they could transform E. coli into an autotroph. To do so, they re-engineered two essential parts of the bacterium’s metabolism: how it gets energy and what source of carbon it uses to grow.
On the energy side, the researchers couldn’t give the bacterium the ability to carry out photosynthesis, because the process is too complex. Instead, they inserted the gene for an enzyme that enabled the microbe to eat formate, one of the simplest carbon-containing compounds, and one other strains of E. coli can’t eat. The microbes could then transform the formate into ATP, an energy-rich molecule that cells can use. That diet gave the microbe the energy it needed to use the second batch of three new enzymes it received—all of which enabled it to convert CO2 into sugars and other organic molecules. The researchers also deleted several enzymes the bacterium normally uses for metabolism, forcing it to depend on the new diet to grow.
The changes didn’t initially produce bacteria capable of living on formate and CO2, however. The researchers suspected the nutrients were still being directed toward its natural metabolism. So, they placed batches of the engineered E. coli in vessels that allowed them to carefully control the microbe’s diet. The team started with basically a starvation diet of xylose, a sugar, along with formate and CO2. This allowed the microbes to at least survive and reproduce.
It also set the stage for evolution: If any bacterial offspring acquired genetic mutations that allowed them to thrive on that diet, they would produce more offspring than those that didn’t evolve. The researchers steadily decreased the amount of xylose available to the microbes as well. After 300 days and hundreds of generations of mutating E. coli, the xylose was gone. Only those bacteria that had evolved into autotrophs survived.
In all, the evolved bacteria picked up 11 new genetic mutations that allowed them to survive without eating other organisms, the team reports today in Cell. “It really shows how amazing evolution can be, in that it can change something so fundamental as cellular metabolism,” Milo says.
“I bow to them for making it succeed,” says Pam Silver, a systems biologist at Harvard Medical School in Boston, who devoted years to a similar project.
Scientists have previously developed dozens of tools to manipulate E. coli’s genes so that it produces different compounds, such as pharmaceuticals and fuels. That means researchers should be able to insert these changes into autotrophic E. coli that eat formate, which is readily made by zapping CO2 in water with electricity. As a result, formate produced from wind and solar power could help engineered bacteria make ethanol and other fuels, or pharmaceuticals, such as the malaria-fighting drug artemisinin. Not bad for a makeover.