Microbial production of human milk fat substitutes: a review

Human milk fat substitutes (HMFS) are designed to replicate the unique structural and nutritional properties of human milk lipids, especially triacylglycerols enriched with sn-2 palmitic acid that enhance infant fat and calcium absorption. Conventional HMFS production relies on enzymatic interesterification of plant oils, but these methods remain costly, palm oil-dependent, and prone to acyl migration. Microbial biosynthesis has emerged as a sustainable alternative, enabling the de novo or substrate-assisted formation of structured lipids with human milk-like stereochemistry. This review consolidates recent advances in microbial HMFS research, focusing on oleaginous bacteria (Rhodococcus opacus, Corynebacterium glutamicum), microalgae (Nannochloropsis oculata, Isochrysis galbana, Schizochytrium sp.), and yeasts (Yarrowia lipolytica, Trichosporon cutaneum). Strategies ranging from substrate engineering and metabolic pathway reconstruction to lipase-mediated acidolysis are evaluated, alongside analytical methods for structural verification. Beyond technical progress, the environmental and industrial implications of microbial HMFS are discussed, including the reduction of palm oil dependency and alignment with sustainability goals. Remaining challenges include achieving consistent sn-2 palmitate enrichment, improving volumetric yields, and navigating regulatory frameworks. Overall, microbial platforms present a promising frontier for the scalable and sustainable production of structured lipids tailored for infant nutrition.