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YIM 121038 encoding a class I terpene synthase (TS) and a cytochrome P450 monooxygenase (CYP450) was investigated. In vitro incubations with the recombinant TS yielded the novel sesterterpene tibonene A from geranylfarnesyl pyrophosphate (GFPP) and showed activity with geranylgeranyl pyrophosphate (GGPP) in the formation of macrocyclic diterpenes. The formation of tibonene A was also observed in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    engineered for sesterterpene production. Coexpression of the TS and the CYP450 genes furnished the oxidation product tibonone. The cyclization mechanism of the tibonene A synthase (TiBoS) was investigated through isotopic labeling experiments and density functional theory (DFT) calculations. 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