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Fig 1.

Example monoterpene compounds, their carbocation precursors, and skeletons.

Product precursor carbocations are quenched by phosphorylation, deprotonation, or hydration to yield products.

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Fig 2.

The iGen algorithm.

(a) Schematic overview. Red modules can be run in parallel on multiple computer cores. (b) Reaction types applied to the carbocations, obtained from mechanistic studies of terpenoid synthases.

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Fig 3.

Example output of iGen, starting from one cyclized carbocation.

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Fig 4.

All monoterpene skeletons identified by iGen.

Red skeletons have products associated with EC numbers.

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Fig 5.

a) Scatter plot of log(ncarbocation) versus the number of steps in the shortest reaction route from the linear substrate to the product skeletons. Red dots indicate skeletons that have products associated with EC numbers. The remaining skeletons (black) have not, to our knowledge, been observed in characterized monoterpenoid natural products. “step 1” is creation of the trans linear carbocation, and “step 2” represents trans/cis isomerization (which does not create cyclized skeletons). Therefore, cyclic skeletons are generated from “step 3”. b) Zoom-in view of the circled region in (a), with the structures of the skeletons depicted. For additional details, see S3 Fig.

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