Metabolic Engineering Strategies for Sustainable Production of High-Value Gyrinops Agarwood Metabolites

Agarwood is a high-value resin formed in the heartwood of certain trees, mainly species of Aquilaria and Gyrinops . It is valued for its complex fragrance and strong cultural and spiritual significance. Among these trees, Gyrinops spp. are important in Indonesia, but their biosynthetic pathways remain less understood than those of Aquilaria . At the same time, rising global demand, slow, unpredictable resin formation, and overexploitation have raised serious concerns about the long-term sustainability of agarwood resources. As a result, the international trade of all agarwood-producing species is strictly regulated. In this review, the potential of synthetic biology and metabolic engineering to support more sustainable agarwood production is examined, with a particular focus on Gyrinops . The chemical and biological basis of agarwood formation is discussed, especially on the production of oxygenated sesquiterpenes and 2-(2-phenylethyl)chromones (PECs). In vitro systems, together with fungal or chemical elicitation, are also evaluated as tools for metabolite production and biosynthetic gene discovery. In addition, the potential of heterologous hosts, including Saccharomyces cerevisiae , Yarrowia lipolytica , Chlamydomonas reinhardtii , and Nicotiana spp., is considered to produce agarwood high-value metabolites. In silico and AI-driven approaches are further highlighted as tools to accelerate the identification and optimization of key Gyrinops biosynthetic genes. Overall, the metabolic engineering approach in Gyrinops agarwood is positioned not as a replacement for natural agarwood production but as a complementary strategy to support conservation, sustainable cultivation, and responsible use of agarwood resources.