Metabolic Engineering of Saccharomyces cerevisiae for Production of Fragrant Terpenoids from Agarwood and Sandalwood

Sandalwood and agarwood essential oils are rare natural comprising fragrant terpenoids that have been used in perfumes incense for millennia. Increasing demand these terpenoids, coupled with difficulties isolating them from sources, led to an interest finding alternative production platforms. Here, we engineered the budding yeast Saccharomyces cerevisiae produce sandalwood agarwood. Specifically, constructed strain FPPY005_39850, which overexpresses all eight genes mevalonate pathway. Using this as background strain, screened seven distinct terpene synthases agarwood, sandalwood, related plant species their activities context of yeast. Five including α-santalene, α-humulene, δ-guaiene, α-guaiene, β-eudesmol. To our knowledge, is first demonstration β-eudesmol We further improved titers by downregulating ERG9, a key enzyme competing pathway, well employing fusions. Our final strains produced at up 101.7 ± 6.9 mg/L. envision work will pave way scalable route establish S. versatile platform high-value chemicals.