From Gene to Protein: Advances and Challenges in Microbial Production of Immunoglobulins

Immunoglobulins exhibit important biological functions, including the neutralization of cytotoxins, enhancement of phagocytic activity, and activation of the complement system, which have driven their widespread application in both the food and pharmaceutical industries. Due to their low cost and short production cycles, microbial expression systems such as bacteria and yeast have been increasingly developed in recent years for immunoglobulin production. However, microbial systems face considerable challenges in ensuring proper protein folding, accurate chain assembly, and the soluble expression of full-length immunoglobulins. Recent optimization strategies have focused on host engineering (e.g., modulating secretion pathways and chaperone proteins), the coordinated regulation of expression elements (e.g., optimizing the light-to-heavy chain ratio), and regulation of fermentation processes. In addition to summarizing the above strategies, this review discusses the progress made in expressing both full-length immunoglobulins and antibody fragments across different microbial hosts, analyzes the advantages and limitations of each system, and explores potential future directions, aiming to provide a reference for the efficient heterologous expression of immunoglobulins.