Sandalwood essential oil has been widely used not only as natural medicines but also in perfumery and
food industries, with sesquiterpenoids as its major components including (Z)- a-santalol and (Z)-bsantalol and so on. The mature heartwoods of Santalum album, Santalum austrocaledonicum and
Santalum spicatum are the major plant resources for extracting sandalwood essential oil, which have been
overexploited. Synthetic biology approaches have been successfully applied to produce natural products
on large scale. In this review, we summarize biosynthetic enzymes of santalenes and santalols, including
various santalene synthases (STSs) and cytochrome P450 monooxygenases (CYPs), and then highlight the
advances of biotechnological production of santalenes and santalols in heterologous hosts, especially
metabolic engineering strategies for constructing santalene- and santalol-producing Saccharomyces
cerevisiae.