Benzylisoquinoline alkaloids (BIAs) are a class of natural compounds found in plants of the Ranunculaceae family, known for their diverse pharmacological activities. However, the extraction yields of BIAs from plants are limited, and the cost of chemical synthesis is prohibitively high. Recent advancements in systems metabolic engineering and genomics have made it feasible to use microbes as bioreactors for BIAs production. This review explores recent progress in enhancing the production and yields of BIAs in two microbial systems: Escherichia coli and Saccharomyces cerevisiae. It covers various BIAs, including (S)-reticuline, morphinane, protoberberine, and aporphine alkaloids. The review provides strategies and technologies for BIAs synthesis, analyzes current challenges in BIAs research, and offers recommendations for future research directions.
Keywords: Benzylisoquinoline alkaloids (BIAs); Microbial cell factories; Natural products; Synthetic biology; Systems metabolic engineering.