New method enables bacteria to produce more chemicals

Scientists have developed a new technique that manipulates bacteria to produce up to 30-fold more quantities of chemicals.
The advance is a big step toward a future in which the predominant chemical factories of the world are colonies of genetically engineered bacteria.
A team of researchers led by Harvard geneticist George Church at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) modified the genes of bacteria in a way that lets them programme exactly what chemical they want the cells to produce - and how much - through the bacteria's metabolic processes.
The concept of metabolic engineering, or manipulating bacteria to synthesise useful chemicals, is not new.

However, the new findings demonstrate a technique that allows scientists to tap an almost endless list of chemicals they can produce using any type of bacteria, such as the common E coli, which was used in the study.
Most promising, the production timescale is nearly 1,000-fold faster than the methods currently used for metabolic engineering, 'Harvard Gazette' reported.

"This advance has implications for pharmaceutical, biofuel, and renewable chemical production," said Wyss Institute Founding Director Donald Ingber.
"By increasing the production output by such a huge factor, we would not only be improving current chemical production but could also make economical production of many new chemicals attainable," Ingber said.

The team uses evolutionary mechanisms to trick the bacteria into self-eliminating the cells that are not high-output performers.
"We make the bacteria addicted to the chemicals we want them to produce," said Jameson Rogers, a lead co-author of the study, Graduate School of Arts and Sciences PhD candidate at Harvard School of Engineering and Applied Science, and Wyss Institute graduate researcher.
"Then, we treat them with an antibiotic that only allows the most productive cells to survive and make it on to the next round of evolution," Rogers said.
The technique makes a desired chemical product essential to the bacteria's survival by modifying their DNA so that antibiotic-resistant genes are activated, but only in the presence of a certain chemical, such as the one that is desired for production.

At the same time, the genetic modification makes the low-output chemical producers highly susceptible to being killed off by antibiotics.
Only the most productive cells generate enough of the desired chemical to be completely resistant to the antibiotic and survive to the next round of evolution.
As each evolution cycle progresses, the bacteria become more and more effective at producing the desired chemical as they use the "survival of the fittest" principle to stamp out the weakest producer cells.
The research was published in the Proceedings of the National Academy of Sciences (PNAS).