[Recent advances in the application value and biosynthesis of chiral reticuline]

Chiral reticuline serves as the core skeleton molecule in the biosynthetic pathway of benzylisoquinoline alkaloids (BIAs). Its efficient and highly selective biosynthesis is crucial for overcoming the limitations of natural extraction and enabling the large-scale production of BIAs. Recent advances in synthetic biology and metabolic engineering have led to significant breakthroughs in the heterologous production of chiral reticuline and BIAs in microbial hosts. However, the biosynthesis of (R)-reticuline remains constrained by the stereoselectivity of key enzymes, necessitating resolution through strategies such as enzyme engineering and pathway reconstitution. Studies on Nelumbo nucifera revealing an (R)-stereochemical preference offer novel pathways for synthesizing (R)-configured BIAs. This review systematically summarizes the application value of chiral reticuline as a key scaffold of BIAs, its synthetic pathways, and the latest research progress. We critically analyze current challenges and propose future research directions, aiming to provide both theoretical support and practical guidance for developing next-generation high-efficiency, high-selectivity BIAs.