Metabolic Engineer Synthesizes Key Breast Milk Sugar
A microbial engineer has synthesized a sugar in human milk that is thought to protect babies from pathogens
The sugar called 2-fucosyllactose, or 2FL, is a human milk oligosaccharide (HMO) which has not been added to any infant formula because the HMO is incredibly expensive to produce.
"We know these oligosaccharides play a vital role in developing a breast-fed baby's gut microbiota and in strengthening their immunity. And 2FL is the most abundant HMO in breast milk," said Michael Miller, a University of Illinois professor of food microbiology.
In order to learn more about the HMO's function, Miller would like to do research with 2FL and newborn piglets, an excellent animal model for the human infant. Unfortunately, 1 milligram of 2FL costs $100, therefore, a single study would require $1 million for the HMO ingredient alone.
However, Yong-Su Jin, a departmental colleague and professor in the University of Illinois Institute for Genomic Biology, believed he could synthesize the breast milk oligosaccharide using an engineered strain of E. coli. Additionally, a postdoctoral researcher in Jin's laboratory had done similar work in Korea. So, combining their experienced staff and expertise, they were able to engineer an HMO that can be produced very cheaply and quickly, making it possible to produce 2FL in the lab, allowing Miller's piglet research.
"E. coli makes a starting material for 2FL as part of its normal metabolism, and that suggested to us that it was possible to use E. coli to produce 2FL," Jin said.
"We increased the production of the starting material (GDP-fucose), by getting E. coli to overexpress the pre-existing biosynthetic pathway. Then we had to transfer GDP-fucose to lactose. We solved that problem by engineering a gene into another organism," Jin explained.
They developed an E. coli mutant that can assimilate lactose. "Because the engineered mutant cannot use the lactose for its own growth, it instead uses lactose to make great quantities of 2FL, the HMO that many researchers want to study," said Jin.
Miller will soon begin a study of the role of 2FL in infant nutrition to assess whether it should be added to infant formula. Miller: "We can also use this technique to synthesize and study the hundreds of other HMOs in human milk."
The research potentially has other useful potential unrelated to infant nutrition.
Jin and Miller believe that their work has military applications. Jin: "Adding 2FL to the food of soldiers on deployment could keep them out of sick bay. More than half of all soldiers in the field are incapacitated at some point with diarrheal illness caused by Campylobacter jejuni."
A second use might be a reduction in the number of Campylobacter infections that originate in raw or undercooked poultry.
Miller: "If chickens consumed poultry feed containing 2FL, pathogens would bind to this oligosaccharide instead of the mucosal lining of the bird's intestine and be eliminated well before the chicken arrived at your supermarket."
"Whole cell biosynthesis of a functional oligosaccharide, 2'-fucosyllactose, using engineered Escherichia coli" was published in Microbial Cell Factories and is available online at http://www.microbialcellfactories.com/content/11/1/48.
Co-authors with Jin and Miller are Won Heong Lee, Panchalee Pathanibul, and Josh Quarterman of the U of I, Nam Soo Han of Chungbuk National University in Korea, and Jung-Hyun Jo and Jin-Ho Seo of Seoul National University in Korea. Jin and Lee are affiliated with the U of I's Institute for Genomic Biology, and Lee is also affiliated with Seoul National University.
Original article: http://research.aces.illinois.edu/content/metabolic-engineer-synthesizes-key-breast-milk-ingredient-makes-research-possible