Production of human milk fat substitute by engineered strains of Yarrowia lipolytica

A - Papers appearing in refereed journals

Bhutada, G., Menard, G. N., Bhunia, R. K., Hapeta, P. P., Ledesma-Amaro, R. and Eastmond, P. J. 2022. Production of human milk fat substitute by engineered strains of Yarrowia lipolytica. Metabolic Engineering Communications. 14 (June), p. e00192. https://doi.org/10.1016/j.mec.2022.e00192

AuthorsBhutada, G., Menard, G. N., Bhunia, R. K., Hapeta, P. P., Ledesma-Amaro, R. and Eastmond, P. J.
Abstract

Human milk fat has a distinctive stereoisomeric structure where palmitic acid is esterified to the middle (sn-2) position on the glycerol backbone of the triacylglycerol and unsaturated fatty acids to the outer (sn-1/3) positions. This configuration allows for more efficient nutrient absorption in the infant gut. However, the fat used in most infant formulas originates from plants, which exclude palmitic acid from the sn-2 position. Oleaginous yeasts provide an alternative source of lipids for human nutrition. However, these yeasts also exclude palmitic acid from the sn-2 position of their triacylglycerol. Here we show that Yarrowia lipolytica can be engineered to produce triacylglycerol with more than 60% of the palmitic acid in the sn-2 position, by expression of lysophosphatidic acid acyltransferases with palmitoyl-Coenzyme A specificity. The engineered Y. lipolytica strains can be cultured on glycerol, glucose, palm oil or a mixture of substrates, under nitrogen limited condition, to produce triacylglycerol with a fatty acid composition that resembles human milk fat, in terms of the major molecular species (palmitic, oleic and linoleic acids). Culture on palm oil or a mixture of glucose and palm oil produced the highest lipid titre and a triacylglycerol composition that is most similar with human milk fat. Our data show that an oleaginous yeast can be engineered to produce a human milk fat substitute (β-palmitate), that could be used as an ingredient in infant formulas.

KeywordsMetabolic engineering ; Yarrowia lipolytica; Human milk fat; OPO; β-Palmitate ; Lipids
Year of Publication2022
JournalMetabolic Engineering Communications
Journal citation14 (June), p. e00192
Digital Object Identifier (DOI)https://doi.org/10.1016/j.mec.2022.e00192
Web address (URL)https://www.sciencedirect.com/science/article/pii/S2214030122000013
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeTailoring Plant Metabolism ISP
Publisher's version
Output statusPublished
Publication dates
Online06 Jan 2022
Publication process dates
Accepted03 Jan 2022
PublisherElsevier
ISSN2214-0301

Permalink - https://repository.rothamsted.ac.uk/item/9878q/production-of-human-milk-fat-substitute-by-engineered-strains-of-yarrowia-lipolytica

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