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Contribution of isopentenyl phosphate to plant terpenoid metabolism


Plant genomes encode isopentenyl phosphate kinases (IPKs) that reactivate isopentenyl phosphate (IP) via ATP-dependent phosphorylation, forming the primary metabolite isopentenyl diphosphate (IPP) used generally for isoprenoid/terpenoid biosynthesis. Therefore, the existence of IPKs in plants raises unanswered questions concerning the origin and regulatory roles of IP in plant terpenoid metabolism. Here, we provide genetic and biochemical evidence showing that IP forms during specific dephosphorylation of IPP catalysed by a subset of Nudix superfamily hydrolases. Increasing metabolically available IP by overexpression of a bacterial phosphomevalonate decarboxylase (MPD) in Nicotiana tabacum resulted in significant enhancement in both monoterpene and sesquiterpene production. These results indicate that perturbing IP metabolism results in measurable changes in terpene products derived from both the methylerythritol phosphate (MEP) and mevalonate (MVA) pathways. Moreover, the unpredicted peroxisomal localization of bacterial MPD led us to discover that the step catalysed by phosphomevalonate kinase (PMK) imposes a hidden constraint on flux through the classical MVA pathway. These complementary findings fundamentally alter conventional views of metabolic regulation of terpenoid metabolism in plants and provide new metabolic engineering targets for the production of high-value terpenes in plants.

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Fig. 1: Terpenoid biosynthetic pathways in plants, and in some archaea and bacteria.
Fig. 2: Substrate recognition by AtNudx1.
Fig. 3: Role of Nudx1 and Nudx3 in vivo.
Fig. 4: Effect of Roseiflexus castenholzii MPD overexpression on terpenoid formation in tobacco.
Fig. 5: Effect of overexpression of AtIPK and AtHMGR1 on terpenoid formation in RcMPD-4 tobacco transgenic line.
Fig. 6: Effect of AtPMK and AtHMGR1 overexpression on terpenoid formation in tobacco leaves.


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This work was supported by the USDA National Institute of Food and Agriculture Predoctoral Grant 2017-67011-26076 to L.K.H. and start-up funds from Purdue University to J.R.W. and S.A.K. This work was also supported by the USDA National Institute of Food and Agriculture Hatch Project number 177845.

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J.P.N. and N.D. conceived the project; L.K.H., S.T.T., J.R.W., S.A.K., J.B., J.P.N. and N.D. designed the experiments; L.K.H., S.T.T., J.R.W., J.H.L. and T.C.D. performed the experiments; L.K.H., S.T.T., J.R.W., J.H.L., T.C.D., S.A.K., J.B., J.P.N. and N.D. analysed the data; L.K.H., S.T.T., J.R.W., J.P.N. and N.D. wrote the paper. All authors read and edited the manuscript.

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Correspondence to Joseph P. Noel or Natalia Dudareva.

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Henry, L.K., Thomas, S.T., Widhalm, J.R. et al. Contribution of isopentenyl phosphate to plant terpenoid metabolism. Nature Plants 4, 721–729 (2018).

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