Engineering the stereoisomeric structure of seed oil to mimic human milk fat

A - Papers appearing in refereed journals

Van-Erp, H., Bryant, F. M., Martin-Moreno, J., Michaelson, L. V., Bhutada, G. and Eastmond, P. J. 2019. Engineering the stereoisomeric structure of seed oil to mimic human milk fat. Proceedings of the National Academy of Sciences of the United States of America - PNAS. September, p. 201907915.

AuthorsVan-Erp, H., Bryant, F. M., Martin-Moreno, J., Michaelson, L. V., Bhutada, G. and Eastmond, P. J.
Abstract

Human milk fat substitute (HMFS) is a class of structured lipid that is widely used as an ingredient in infant formulas. Like human milk fat, HMFS is characterised by enrichment of palmitoyl (C16:0) groups specifically at the middle (sn-2 or β) position on the glycerol backbone, and there is evidence that triacylglycerol (TAG) with this unusual stereoisomeric structure provides nutritional benefits. HMFS production currently relies on enzyme-based catalysis since there is no appropriate biological source of fat with the equivalent structure, other than humans. Most of the fat currently used in infant formulas is obtained from plants, which exclude C16:0 from the middle position. In this study we have modified the metabolic pathway for TAG biosynthesis in the model oilseed Arabidopsis thaliana to increase the percentage of C16:0 at the middle (versus outer) positions by more than 20-fold (i.e. from ~3% in wild type to >70% in our final iteration). This level of C16:0 enrichment is comparable to human milk fat. We achieved this by relocating the C16:0-specific chloroplast isoform of the enzyme lysophosphatidic acid acyltransferase (LPAT) to the endoplasmic reticulum so that it functions within the cytosolic glycerolipid biosynthetic pathway to esterify C16:0 to the middle position. We then suppressed endogenous LPAT activity to relieve competition and knocked out phosphatidylcholine:diacylglycerol cholinephosphotransferase activity to promote the flux of newly-made diacylglycerol directly into TAG. Applying this technology to oilseed crops might provide a new source of HMFS for infant formula.

KeywordsMetabolic engineering; Oilseeds; Structured triacylglycerols; Human milk fat
Year of Publication2019
JournalProceedings of the National Academy of Sciences of the United States of America - PNAS
Journal citationSeptember, p. 201907915
Digital Object Identifier (DOI)doi:10.1073/pnas.1907915116
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeTailoring Plant Metabolism ISP
TPM - Tailoring Plant Metabolism - Work package 1 (WP1) - High value lipids for health and industry
Publisher's version
Copyright license
CC BY
Accepted author manuscript
Copyright license
CC BY
Supplemental file
Copyright license
CC BY
Supplemental file
Copyright license
CC BY
Output statusPublished
Publication dates
Online30 Sep 2019
Publication process dates
Accepted04 Sep 2019
PublisherNational Academy of Sciences of the United States of America
ISSN0027-8424

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