E. coli engineered to make serine

RESEARCHERS in Denmark have genetically engineered a strain of Escherichia coli bacteria to make industrial quantities of serine, an amino acid gaining increasing commercial interest.

Serine is used in a wide variety of products, including in moisturisers, cosmetics and tube-feeding formulas. It can be converted into other chemicals such as detergents and plastics, and is thought to be a promising candidate as a feedstock to replace some chemicals currently produced from crude oil. The cheapest way to make amino acids commercially is through the E. coli fermentation. However, large quantities of serine are toxic to the unmodified bacterium. Alex Toftgaard Nielsen, a professor at the Novo Nordisk Foundation Center for Biosustainability at the Technical University of Denmark (DTU Biosustainability), and his team, have now overcome that problem.

The researchers used an automated ‘adaptive laboratory evolution’ (ALE) process. They expose E. coli cells to small amounts of serine. As the intolerant strains die off, only tolerant strains are left. The serine level is gradually increased leaving more and more tolerant bacteria. The process uses highly specialised ALE robots, which monitor the temperature, growth, mortality, cell density and nutrient content of each sample continually. Researcher Hemanshu Mundhada says there are so many samples that it would be impossible for a researcher to perform the tasks manually.

The researchers then genetically modified the tolerant E. coli strains to produce larger amounts of serine, using ordinary sugar or molasses, a residue from sugar production, as feedstock. They achieved a yield of 25–30% of serine compared to the amount of sugar used.

While other bacterial species strains can make serine, they use methanol and glycine, which must be chemically produced and is therefore much more expensive than sugar. At present serine costs around US$30/kg, but the researchers believe that the new technique could bring this down to US$3/kg. At this price, demand is expected to grow significantly, from its present level of around 1,000 t/y.

“This discovery is quite unique and proves that we can actually adapt cells to tolerate large amounts of serine – something many people thought wasn’t possible,” said Nielsen.

The team is now setting up a company to scale up the process and commercialise the technology.

Metabolic Engineering DOI: 10/bw5r