Abstract:Rosmarinic acid(RA) is a multifunctional natural phenolic acid, mainly found in plants of the Lamiaceae and Boraginaceae families. Due to its remarkable antioxidant and anti-inflammatory activities, it has been used across multiple industries widely. To overcome the inherent shortcomings of traditional acquisition methods, the construction of efficient microbial cell factories has become a research hotspot. This article systematically reviews the research progress of heterologous biosynthesis of rosmarinic acid from the perspectives of synthetic biology and metabolic engineering. In terms of synthetic pathways, the strategies for mining, screening and pathway assembly of key genes in different chassis hosts (such as Escherichia coli and Saccharomyces cerevisiae), as well as the engineering modification of related enzymes, were summarized. Regarding the regulation of metabolic networks, the discussion focuses on strategies such as enhancing precursor supply, knocking out competing branch pathways, attenuating byproduct formation, balancing cofactors, and regulating carbon metabolic flux. In addition, this paper also combines the latest research progress in biosynthesis to systematically analyze the main bottlenecks faced by the current microbial synthesis system in terms of yield, stability, cost, and further looks forward to the optimization direction of future biosynthesis of RA, aiming to provide new ideas for the industrial development of this natural product.