Research team engineer plants to produce the human form of key fat molecule

  • 02
  • OCT
  • 2019

Scientists have engineered plants to produce an oil that mimics the chemical structure of human milk fat, a major component of breast milk.

Previous studies suggest the human form of this molecule, triacylglycerol, aids absorption of key nutrients by the infant gut, but few infant formulas contain anything resembling it.

Now a team from Rothamsted Research have found a way to modify the biochemical pathways of plants so they can produce the human form of this key nutrient.

Around half the calories in human milk come from triacylglycerol, and in infant formula this fat is mainly sourced from plants - but vegetable oils have a different chemical structure to the fat produced by mothers in their milk.

It is the uniquely human arrangement of fatty acids - the constituent molecules that make up triacylglycerol - that is thought to provide benefits. These include the absorption of calcium, which is vital for bone development.

Whilst some milk formulas already contain triacylglycerol that mimics the structure of human milk fat, these Human Milk Fat Substitutes (HMFS) are expensive to make, whilst the process generates solvent waste and uses palm oil – the growing of which has been blamed for tropical deforestation.

Costs are one of the main reasons why HMFS are found in only about 10% of infant formulas, particularly premium products formulated and marketed for ease-of-digestion.

Whilst breast milk is the best and first choice for infant nutrition, the team hope their breakthrough could lead to improvement in all grades of formula for babies who need it.

Lead researcher, Dr Peter Eastmond said the oil from the engineered plants has triacylglycerol molecules in this human configuration in similar proportions as found in a mothers’ milk.

“In human milk fat, saturated fatty acids are attached to the middle point of the central ‘backbone’ of the triacylglycerol molecule, giving it a distinctive structure, and evidence from several clinical trials has suggested that this assists nutrient absorption in the infant gut. However, the fat used in most infant formulas is derived from plants, where these saturated fatty acids almost always bond to the ends of the ‘backbone’ instead.”

Writing in the journal Proceedings of the National Academy of Sciences, the team report making triacylglycerol where more than 70% of the saturated fatty acids are in the crucial ‘middle’ position, compared with less than 3% in the unmodified plant – a more than 20-fold increase.

“We have engineered the metabolism of a plant so the fat it produces has the structure found in human milk, not vegetable oil,” said Dr Eastmond.

The infant formula market is currently estimated to use nearly half a million metric tons of vegetable-derived fat per year.

According to Dr Eastmond, applying metabolic engineering technology to oil producing crops, or even oil producing microorganisms, might provide a new source of cost-effective, human milk fat substitute for infant nutrition.

“Several oilseed crops could be candidates for HMFS production, such as sunflower and oilseed rape.”

In this BBSRC-funded study, the team modified the genes responsible for a metabolic pathway in the oilseed plant Arabidopsis thaliana, a species often used as a test bed in biological research, to demonstrate it could be done.

They relocated an enzyme, lysophosphatidic acid acyltransferase (LPAT), from where it usually resides within the cell’s light-capturing chloroplasts, to the endoplasmic reticulum, an area of the cell where fats are made.

This led to LPAT being incorporated into the fat production pathway, resulting in triacylglycerol produced in the human form.

“Being able to modify the metabolic pathways of plants opens many potential doors and demonstrates how similar approaches could provide benefits to several different sectors, including human health and the environment,” Dr Eastmond said.

This work was funded by the UK Biotechnology and Biological Sciences Research Council through Grant BB/ P012663/1

About Rothamsted Research
Rothamsted Research is the longest-running agricultural research institute in the world. We work from gene to field with a proud history of ground-breaking discoveries, from crop treatment to crop protection, from statistical interpretation to soils management. Our founders, in 1843, were the pioneers of modern agriculture, and we are known for our imaginative science and our collaborative influence on fresh thinking and farming practices.
Through independent science and innovation, we make significant contributions to improving agri-food systems in the UK and internationally. In terms of the institute’s economic contribution, the cumulative impact of our work in the UK was calculated to exceed £3000 million a year in 20151. Our strength lies in our systems approach, which combines science and strategic research, interdisciplinary teams and partnerships.
Rothamsted is also home to three unique resources. These National Capabilities are open to researchers from all over the world: The Long-Term Experiments, Rothamsted Insect Survey and the North Wyke Farm Platform.
We are strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), with additional support from other national and international funding streams, and from industry. We are also supported by the Lawes Agricultural Trust (LAT).
For more information, visit; Twitter @Rothamsted
1Rothamsted Research and the Value of Excellence: A synthesis of the available evidence, by Séan Rickard (Oct 2015)

The Biotechnology and Biological Sciences Research Council is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £469 million in world-class bioscience in 2016-17. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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About LAT
The Lawes Agricultural Trust, established in 1889 by Sir John Bennet Lawes, supports Rothamsted Research’s national and international agricultural science through the provision of land, facilities and funding. LAT, a charitable trust, owns the estates at Harpenden and Broom's Barn, including many of the buildings used by Rothamsted Research. LAT provides an annual research grant to the Director, accommodation for nearly 200 people, and support for fellowships for young scientists from developing countries. LAT also makes capital grants to help modernise facilities at Rothamsted, or invests in new buildings.