Berkeley, California, USA
June 13, 2024
New research shows that plants may be the secret to improving commercial infant formula
Human breast milk contains a unique blend of sugars and proteins tailored to meet the needs of growing infants, including approximately 200 complex sugar molecules that help prevent disease and support the growth of healthy gut bacteria. Unfortunately, these complex sugars are tricky to manufacture, and commercial baby formulas contain only a fraction of the amount found in human breast milk.
IGI Investigator Patrick Shih
In a new study published today in the journal Nature Food, researchers show how plants’ sugar-making machinery can be hijacked to produce a diverse array of these human milk sugars, also called human milk oligosaccharides. The findings could lead to healthier and more affordable formula for babies, or more nutritious non-dairy plant milks for adults.
“Plants are these phenomenal organisms that take sunlight and carbon dioxide from our atmosphere and use them to make sugars. And they don’t just make one sugar — they make a whole diversity of simple and complex sugars,” said study senior author Patrick Shih, an assistant professor of plant & microbial biology and an investigator at the Innovative Genomics Institute at the University of California, Berkeley. “We thought, since plants already have this underlying sugar metabolism, why don’t we try rerouting it to make human milk oligosaccharides?”
All complex sugars — including human milk oligosaccharides — are made from “building blocks” of simple sugars, called monosaccharides, which can be linked together to form an vast array of chains and branched chains. What makes human milk oligosaccharides unique are the specific set of linkages, or rules for connecting simple sugars together, that are found in these molecules.
If we could start making these larger, more complex human milk oligosaccharides, we could solve a problem that that industry currently can’t solve.
To convince plants to make human milk oligosaccharides, study first author Collin Barnum engineered the genes responsible for the enzymes that make these specific linkages. Working with Daniela Barile, David Mills and Carlito Lebrilla at the University of California, Davis, he then introduced the genes into the Nicotiana benthamiana plant, a close relative of tobacco.
The genetically modified plants produced 11 known human milk oligosaccharides, along with a variety of other complex sugars with similar linkage patterns.
A Nicotiana benthamiana plant that has been genetically modified to produce human milk oligosaccharides. (Photo: Collin Barnum)
“We made all three major groups of human milk oligosaccharides,” Shih said. “To my knowledge, no one has ever demonstrated that you could make all three of these groups simultaneously in a single organism.”
Barnum then worked to create a stable line of N. benthamiana plants that were optimized to produce a single human milk oligosaccharide called LNFP1.
“LNFP1 is a five-monosaccharide-long human milk oligosaccharide that is supposed to be really beneficial, but so far cannot be made at scale using traditional methods of microbial fermentation,” said Barnum, who completed the work as a graduate student at UC the University of California, Davis. “We thought that if we could start making these larger, more complex human milk oligosaccharides, we could solve a problem that that industry currently can’t solve.”
Currently, a small handful of human milk oligosaccharides can be manufactured using engineered E. coli bacteria. However, isolating the beneficial molecules from other toxic byproducts is a costly process, and only a limited number of baby formulas include these sugars in their mixtures.
As part of the study, Shih and Barnum worked with collaborator Minliang Yang at North Carolina State University to estimate the cost of producing human milk oligosaccharides from plants at an industrial scale, and found that it would likely be cheaper than using microbial platforms.
“Imagine being able to make all the human milk oligosaccharides in a single plant. Then you could just grind up that plant, extract all the oligosaccharides simultaneously, and add that directly into infant formula,” Shih said. “There would be a lot of challenges in implementation and commercialization, but this is the big goal that we’re trying to move towards.”
Additional authors include Bruna Paviani, Garret Couture, Chad Masarweh, Ye Chen, Yu-Ping Huang, David A. Mills, Carlito B. Lebrilla and Daniela Barile of UC Davis; Kasey Markel of UC Berkeley; and Minliang Yang of North Carolina State University.
This work was supported in part by the National Institutes of Health (NIGMS T32 Training Program), the U.S. Department of Energy and the National Center for Complementary and Integrative Health (R00AT009573)
The original version of this article was published by Berkeley News
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