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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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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Author notes

  1. These authors contributed equally to this work: Laura K. Henry, Suzanne T. Thomas.


  1. Department of Biochemistry, Purdue University, West Lafayette, IN, USA

    • Laura K. Henry
    • , Joseph H. Lynch
    •  & Natalia Dudareva
  2. Jack H Skirball Center for Chemical Biology and Proteomics, Salk Institute for Biological Studies, La Jolla, CA, USA

    • Suzanne T. Thomas
    •  & Joseph P. Noel
  3. Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN, USA

    • Joshua R. Widhalm
    •  & Natalia Dudareva
  4. Purdue Center for Plant Biology, Purdue University, West Lafayette, IN, USA

    • Joshua R. Widhalm
    • , Sharon A. Kessler
    •  & Natalia Dudareva
  5. Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN, USA

    • Thomas C. Davis
    •  & Sharon A. Kessler
  6. Michael Smith Laboratories, University of British Columbia, Vancouver, Canada

    • Jörg Bohlmann
  7. Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA

    • Joseph P. Noel


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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.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Joseph P. Noel or Natalia Dudareva.

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