Biosynthesis, enzymatic basis, and transcriptional regulation of benzylisoquinoline alkaloids in medicinal plants

Abstract

Benzylisoquinoline alkaloids (BIAs) are a class of structurally diverse secondary metabolites, with over 2,500 identified variants classified into seven major categories based on their core skeletons. These compounds exhibit significant pharmacological activities – including antitumor, antibacterial, and anti-inflammatory effects – and serve as important sources of clinical drugs such as morphine, berberine, and magnoflorine. Currently, BIAs are primarily obtained through plant cultivation and extraction. However, factors such as low in-planta content, seasonal constraints, and environmental variability contribute to vulnerabilities in the supply chain. In light of these challenges, microbial biosynthesis using engineered strains (e.g., yeast) has emerged as a promising alternative, though it requires complete elucidation and functional expression of all pathway enzymes. Enhancing BIAs production in crops through transcriptional regulation – targeting key enzymes, transcription factors (such as WRKY, bHLH, and AP2/ERF families), and phytohormone signaling – represents a feasible interim strategy. Advanced approaches, including coexpression of enzyme genes and transcription factors, hold promise for accelerating the development of industrial-scale alkaloid-producing cell factories and crop improvement, thereby enabling sustainable drug supply.