Precision Fermentation for Animal Identical Dairy Proteins: A Multi Disciplinary Review of Microbial Engineering, Process Intensification, Safety, and Environmental Aspects

Abstract

The dairy industry is under growing pressure to reduce its environmental footprint, improve animal welfare, and meet the needs of lactose‑intolerant consumers. Precision fermentation (PF) has emerged as a biotechnological strategy to produce molecularly identical milk proteins – including β‑lactoglobulin, α‑lactalbumin, caseins, and lactoferrin – using genetically engineered microorganisms. This review provides an extended and critical synthesis of the PF dairy protein field based on 75 peer‑reviewed sources, including recent advances (2020–2026) and complementary insights from nanotechnological decontamination and plant‑based safety assessments. We compare five microbial host platforms (Komagataella phaffii, Saccharomyces cerevisiae, Kluyveromyces lactis, Aspergillus oryzae, and Escherichia coli) with respect to titre, folding fidelity, secretion efficiency, and regulatory status. Fed‑batch fermentation in bioreactors up to 150,000 L is evaluated, and downstream processing trains (centrifugation, depth filtration, cation exchange, ultrafiltration, spray drying) are described with real‑world yield data. A dedicated safety section examines residual host‑cell DNA, endotoxins, and allergenicity. We integrate life cycle assessment (LCA) and techno‑economic analysis (TEA) to identify the conditions under which PF dairy becomes cost‑competitive and environmentally superior. Finally, we embed the discussion within broader food safety concerns – including heavy metal contamination of raw materials – drawing on recent studies from Iran and elsewhere. Our conclusions highlight that PF dairy is technically mature but still requires advances in continuous processing, waste‑based feedstocks, and harmonised global labelling to achieve widespread market adoption.