Advances in Synthetic Biochemistry Could Lead to Biofuel Production

A team of biochemists from UCLA have created a method to convert sugar into a range of useful chemical compounds, without the use of cells. These chemical compounds could potentially be applied in the manufacture of new pharmaceuticals and biofuels.

The idea of synthetic biology is to redesign cells so they will take sugar and run it through a series of chemical steps to convert it into to a biofuel or a commodity chemical or a pharmaceutical. However, that’s extremely difficult to do. The cell protests. It will take the sugar and do other things with it that you don’t want, like build cell walls, proteins and RNA molecules. The cell fights us the whole way.

James Bowie, Professor of Biochemistry and Chemistry, UCLA

Bowie and his team created a promising method as an alternative, which he refers to as synthetic biochemistry, that bypasses the requirement for cells.

We want to do a particular set of chemical transformations — that’s all we want — so we decided to throw away the cells and just build the biochemical steps in a flask. We eliminate the annoying cell altogether.

James Bowie, Professor of Biochemistry and Chemistry, UCLA

The team purified over 24 enzymes in specific concentrations and combinations, placed them in a flask, and added glucose to the flask. The pathways and enzymes created in Bowie’s laboratory are not easily available in nature. "When we don’t have to worry about keeping cells happy, it’s easier to rearrange things the way we want,” he said.

If the enzymes are not good enough — not fast enough, not stable enough — then we re-engineer them.

Tyler Korman, Postdoctoral Scholar, UCLA

The study was published in the Nature Chemical Biology journal, which illustrates that the UCLA team can produce complex enzyme systems without the cell, and that those systems can operate adequately for use in the manufacture of commodity chemicals and biofuels.

Bowie, a member of the UCLA–Department of Energy Institute’s Division of Systems Biology and Design and UCLA’s Molecular Biology Institute, stated that synthetic biochemistry can be applied in several industrial products, including in the manufacture of flavors, plastics, and scents. It could later be even applied in biofuels.

Usually bioengineers require cells to change 100% of the sugar into fuel. Yeast fermentation in about a 70% yield can produce ethanol via the same process applied to manufacture wine and beer, “but that’s after effectively thousands of years of optimization by man to increase alcohol levels in our favorite drinks,” Bowie said. He added that the excellent yields for cell-produced chemicals in bioengineered strains are normally very limited or possess other issues.

Bowie, Korman and Paul Opgenorth, another postdoctoral scholar in the laboratory, state that they have accomplished nearly a 90% yield for the manufacture of a biodegradable plastic.

Going forward, the team will continue to work on overcoming any challenges that still exist, including controlling the manufacture of high-energy molecules required for biochemical reactions.

In a significant introduction to the current research, the team reported in the Nature Communications journal (June 17, 2014 issue) a key development in controlling these high energy molecules — a system the biochemists referred to as a molecular purge valve — and are continuing to expand other “tricks” for regulations.

We have to make synthetic biochemistry robust enough to work in a very large industrial plant.

James Bowie, Professor of Biochemistry and Chemistry, UCLA

Bowie has conducted research at UCLA since 1989, first as a postdoctoral scholar, and with his own laboratory since 1993.

The researchers are planning to open a company, called Invizyne Technologies, Inc., in which Bowie will be a scientific adviser.

The U.S. Department of Energy federally funded the study.