Biosynthesis and regulatory mechanisms of benzylisoquinoline alkaloids in medicinal plants

Benzylisoquinoline alkaloids (BIAs) derived from Coptis species, opium poppy, and California poppy have been demonstrated to cure various diseases. Historically, Coptis species, opium poppy, and California poppy have served as models for the study of BIAs; however, the produced BIAs in these plants are of low yield for medicinal purposes. Although the chemical synthesis approach has been adopted for large-scale production of BIAs, medicinal plants remain the only reliable platform for this purpose. With the recent advancement of high-throughput sequencing technology, genomic or transcriptomic information of Coptis chinensis, Coptis deltoidea, Coptis teeta, opium poppy, and California poppy has been available over the past decade, which has led to a comprehensive elucidation and update of the biosynthetic pathways of BIAs and regulatory mechanisms governing BIA production. The jasmonate-independent and jasmonate-dependent regulatory pathways, triggered by external elicitors, are demonstrated in this study. Overexpression of AP2/ERF transcription factor, base editing for key enzymes of tyrosine synthesis, and transport engineering in microbes are some strategies presented to provide ideas for enhancing BIAs content. This review provides a foundation for BIA accumulation in medicinal plants and de novo synthesis of BIAs in microbial hosts, thereby facilitating the discovery and development of alkaloid-based drugs.