Two-step pathway for isoprenoid synthesis

Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):506-511. doi: 10.1073/pnas.1812935116. Epub 2018 Dec 24.


Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.

Keywords: biosynthesis; isopentenol; isoprenoids; pathway; utilization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Escherichia coli K12 / genetics
  • Escherichia coli K12 / metabolism*
  • Glucose / genetics
  • Glucose / metabolism
  • Terpenes / metabolism*


  • Terpenes
  • Glucose