Rosmarinic acid (RA) is a high-value natural compound, which was initially isolated from Rosmarinus officinalis L. in 1958 [1]. RA is found in various medicinal herbs, and its occurrence has been specifically documented in the Nepetoideae subfamily, with notable examples including Thymus mastichina, Ocimum sanctum, and Hyptis pectinata [2]. A phenolic acid with notable bioactivity, RA is a natural ester of caffeic acid and 3,4-dihydroxyphenyllactic acid (3,4-DHPL) that has antimicrobial, anti-inflammatory, and anticarcinogenic properties [3], [4]. It plays a significant role in preventing cancer and diabetes [5] and has potential remedy for alcoholic liver disease [6]. Additionally, it demonstrates promising bioactivities, including anxiolytic effects and cardioprotective properties [7]. As an antioxidant, RA effectively scavenges free radicals, complexes with pro-oxidant ions, inhibits lipid peroxidation, and binds to biomolecules [8]. It has also been shown to improve breast disease by reducing pro-inflammatory cytokine levels [9]. Unlike traditional anti-inflammatory drugs, RA is a natural anti-inflammatory pharmaceutical ingredient, aligning with the growing demand for sustainable health solutions [10]. It has been shown to exhibit a wide range of bioactivities, thus attracting significant global interest. Due to its diverse benefits, RA is useful in the pharmaceutical, food, and cosmetic industries [11], [12]. With its rising applications, global RA production has surged, and the market is projected to grow by 10 % annually, driven primarily by pharmaceutical and cosmetic demands. Its applications are summarized in Fig. 1.

The global RA market is projected to grow significantly, with a predicted compound annual growth rate of 9.1 % from 2025 to 2035. By 2035, the total market value is expected to reach US$ 369.7 million (https://www.futuremarketinsights.com/reports/rosmarinic-acid-market). The prediction means the wide application potential of RA in the market. However, the growing market demand for RA is impeded by the inefficiencies of traditional production methods. Conventional strategies, including physical or chemical extraction from plants, chemical synthesis, and plant tissue culture, may be associated with high costs, low yields, and environmental pollution [13]. The yield of RA from plants depends heavily on growth conditions, which are influenced by uncontrollable factors such as light and precipitation [14]. Furthermore, the cultivation of RA-producing plants is typically confined to warm, humid coastal regions, limiting scalability and sustainability. Extracting RA is particularly expensive when it is present in low concentrations in plants [15]. To overcome these challenges, there has been a notable shift toward bioproduction. Metabolic engineering techniques have enabled the development of microbial cell factories to produce high-value compounds like RA [16]. This approach enhances yield and minimizes waste and pollution compared to traditional methods, promoting sustainability in natural product production [17].

This review systematically explored the application of metabolic engineering in promoting the biosynthesis of RA. It covers four strategies, including the modification of plant metabolic pathways, the reconstruction of metabolic pathways, cofactor engineering, and modular co-culture. Additionally, analysis of techno-economic feasibility and challenges of RA production via metabolic engineering was conducted from three aspects: reducing substrate costs, optimizing metabolic pathways, and scaling up production. This review aimed to provide a reference for subsequent RA-related research and improve the efficiency of RA biosynthesis.