Bioengineered algal lipids enriched in structured medium- and long-chain triacylglycerols, linoleate, and sn-2 palmitate for human milk fat substitutes

Lin, J. Y.-T.; Duenas, M. A.; Kosina, S. M.; Iavarone, A. T.; Khoo, K.; Nicora, C. D.; Purvine, S. O.; Northen, T. R.; Moseley, J. L.; Merchant, S. S.

doi:10.64898/2026.05.15.725531

bioRxiv · 10.64898/2026.05.15.725531

Bioengineered algal lipids enriched in structured medium- and long-chain triacylglycerols, linoleate, and sn-2 palmitate for human milk fat substitutes

Lin, J. Y.-T.·Duenas, M. A.·Kosina, S. M.·Iavarone, A. T.·Khoo, K.·Nicora, C. D.·Purvine, S. O.·Northen, T. R.·Moseley, J. L.·Merchant, S. S.

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Abstract

Triacylglycerols (TAGs) in human milkfat (HMF) provide over 50% of the calories for infant nutrition. Their unique architecture, featuring palmitic acid predominantly esterified at the sn-2 position, facilitates absorption as 2-palmitoyl monoacylglycerol after hydrolysis of the sn-1 and sn-3 fatty acids by gut lipases. Conventional vegetable oil-based infant formulas mimic the HMF fatty acid profile but lack its distinct regioisomeric structure, abundant medium- and long-chain triglycerides (MLCTs), and oleic-to-linoleic acid ratios that vary with maternal diet and geography. We have engineered the oleaginous green alga Auxenochlorella for biosynthesis of TAGs enriched in MLCTs, sn-2 palmitate, and linoleate via heterologous expression of acyl-acyl-carrier-protein (ACP) thioesterases, palmitate-specific lysophosphatidic acid acyltransferases, and lysophosphatidylcholine acyltransferase. These structured algal lipids replicate both the major fatty acid proportions and regioisomeric composition of authentic HMF, providing single-source bioengineered alternatives to plant-derived HMF substitutes for infant formula.

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Lin, J. Y.-T., Duenas, M. A., Kosina, S. M., Iavarone, A. T., Khoo, K., Nicora, C. D., Purvine, S. O., Northen, T. R., Moseley, J. L., Merchant, S. S.. 2026-05-16. Bioengineered algal lipids enriched in structured medium- and long-chain triacylglycerols, linoleate, and sn-2 palmitate for human milk fat substitutes. https://doi.org/10.64898/2026.05.15.725531

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