Characterization of SchTPSs Enables Construction of Yeast for the Bioproduction of α-Cadinol and the Related Sesquiterpenes.

Plant volatile sesquiterpenes (PVSs) play important roles in chemical plant defense. However, it is difficult to isolate sufficient PVSs for deep investigations due to their low contents and chemical and physical properties close to those of other lipids. The extracts of Stellera chamaejasme L. exhibit insecticidal, fungicidal, and allelopathic activities. In this study, we identified three sesquiterpene synthase genes (SchTPS5, SchTPS6, and SchTPS7) from S. chamaejasme L. SchTPS7 is an α-farnesene synthase. SchTPS5 and SchTPS6 are two catalytically promiscuous sesquiterpene synthases, and α-cadinol and τ-muurolol are the predominant products for both of them in Saccharomyces cerevisiae. This study, for the first time, reports plant sesquiterpene synthases capable of producing α-cadinol and/or τ-muurolol in a heterologous host. More intriguingly, seven out of eight products of SchTPS6 in S. cerevisiae possess various insecticidal, fungicidal, and herbicidal activities. Building on this finding, we used SchTPS6 to construct an engineered S. cerevisiae for the production of these sesquiterpenes. The titers of two major products α-cadinol and τ-muurolol, respectively, reached 46.2 ± 4.0 and 11.2 ± 1.4 mg/L in a flask. This study lays a foundation for the development of new agrochemical mixtures.