Harvard Researchers Program Bacteria to Make Precursors for High-Quality Biofuels

A team of Harvard researchers used a rational metabolic engineering approach to modify fatty acid synthesis in the bacterium Escherichia coli in order to increase the production of a specific fatty acid which is a precursor of octane, a high-quality fuel that could one day replace gasoline.

The team's strategy focused on engineering medium chain fatty acids (MCFA) – those with chains of 4 to 12 carbons long – which are associated with improved fuel quality and also known as important industrial precursors. The team specifically targeted the production of an eight-carbon fatty acid called octanoate (or octanoic acid) from which the octane fuel can be derived.

The researchers technically demonstrated the production of MCFAs with chain lengths from 4 to 13 carbons and identified the factors that limit MCFA yield. After finding that elongation rates were too rapid for optimal MCFA production, they genetically engineered fatty acid elongation in E. coli by inhibiting an essential enzyme to slow down the elongation process in response to a chemical inducer, and thereby favor the production of octanoic acid. Testing a set of mutants for their ability to increase carbon flux into fatty acid synthesis allowed the researchers to maximize octanoic acid yield in the engineered strain.

This work led by scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Department of Systems Biology at Harvard Medical School was published in the journal Proceedings of the National Academy of Sciences. Next, they plan to engineer E. coli to convert octanoate and other fatty acids into alcohols, just one chemical step away from octane.