ReviewComprehensive reviews in food science and food safety2026
Toward Rational Design of Precision-Fermented Milk Proteins: Integrating Cross-Species Selection, Post-Translational Modification, and AI Optimization.
Review in Comprehensive reviews in food science and food safety, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Milk proteins deliver nutritional, functional, and bioactive properties that alternative protein sources cannot adequately replicate, yet conventional livestock-based production faces compounding constraints of scalability, resource intensity, and sustainability. Precision fermentation offers a structurally distinct solution, but existing reviews have addressed neither a systematic cross-species framework for target selection nor a treatment of post-translational modifications (PTMs) gap-bridging, leaving critical gaps in rational pipeline design. This review integrates four analyses: a cross-species comparison of sequence, structural, and PTMs characteristics across human, bovine, goat, and camel milk proteins to inform target prioritization; a consolidation of advances in host engineering, fermentation scale-up, and downstream purification; a structural-functional comparison of precision-fermented and native milk proteins encompassing phosphorylation, disulfide bond pairing, and glycosylation fidelity, alongside strategies for bridging identified PTMs gaps; and an evaluation of AI-driven optimization strategies for heterologous milk protein expression. Cross-species analysis favors human-derived sequences for infant nutrition and immunity, while ruminant proteins excel in expression compatibility and scalability. α-Lactalbumin and β-lactoglobulin are the most tractable targets given minimal PTM dependency; caseins and lactoferrin require intracellular phosphorylation and glycosylation unavailable in microbial hosts. AI accelerates process optimization but cannot yet co-optimize yield, folding fidelity, and PTM accuracy, a key frontier for next-generation engineering. Scale-up robustness, glycoengineering consistency, and regulatory definition remain underexplored.
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