Heterologous Expression, Digestive Stability, and Emerging Trends of Lactoferrin.

Lactoferrin is an iron-binding glycoprotein with a wide range of biological functions. Due to its extensive utilization, lactoferrin is extensively used in newborn formula, specialized medical food, and functional food. However, the separation and purification of lactoferrin from milk alone cannot meet the increasing market demand. The other significant concern regarding the applicability of lactoferrin is its ability to withstand gastrointestinal digestion during ingestion. The biosynthetic mechanism of lactoferrin provides a crucial foundation for addressing the aforementioned issues. This work reviews the principal approaches for the heterologous expression of lactoferrin, and, by constructing a multicriteria decision framework, we propose lactoferrin production strategies tailored to specific application scenarios, with a particular emphasis on the machine learning-driven on-demand design concept. The current review article also presents an overview of the opportunities and challenges associated with lactoferrin heterologous expression technology and its effective delivery, with the intention of offering valuable references and guidance for researchers to further investigate the application of lactoferrin heterologous expression in large-scale production. The development of synthetic biological systems has enabled its industrial-scale production. Nevertheless, challenges remain with regard to yield, functional integrity, and compliance. Our review offers a promising insight to meet the growing market demand of lactoferrin and use the latest strategies to enhance its production and nutrition efficiency and stability during digestion.