Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production

Christopher B. Eiben, Tristan De Rond, Clayton Bloszies, Jennifer Gin, Jennifer Chiniquy, Edward E.K. Baidoo, Christopher J. Petzold, Nathan J. Hillson, Oliver Fiehn, Jay D. Keasling

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Lepidoptera (butterflies and moths) make the six-carbon compounds homoisopentenyl pyrophosphate (HIPP) and homodimethylallyl pyrophosphate (HDMAPP) that are incorporated into 16, 17, and 18 carbon farnesyl pyrophosphate (FPP) analogues. In this work we heterologously expressed the lepidopteran modified mevalonate pathway, a propionyl-CoA ligase, and terpene cyclases in E. coli to produce several novel terpenes containing 16 carbons. Changing the terpene cyclase generated different novel terpene product profiles. To further validate the new compounds we confirmed 13C propionate was incorporated, and that the masses and fragmentation patterns were consistent with novel 16 carbon terpenes by GC-QTOF. On the basis of the available farnesyl pyrophosphate analogues lepidoptera produce, this approach should greatly expand the reachable biochemical space with applications in areas where terpenes have traditionally found uses.
Original languageEnglish
JournalACS Synthetic Biology
Volume8
Issue number10
Pages (from-to)2238-2247
Number of pages10
ISSN2161-5063
DOIs
Publication statusPublished - 2019

Keywords

  • Mevalonate pathway
  • Terpenes
  • Juvenile hormones
  • Homoisopentenyl pyrophosphate
  • HIPP
  • Homodimethylallyl pyrophosphate
  • HDMAPP

Cite this

Eiben, C. B., De Rond, T., Bloszies, C., Gin, J., Chiniquy, J., Baidoo, E. E. K., ... Keasling, J. D. (2019). Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production. ACS Synthetic Biology, 8(10), 2238-2247. https://doi.org/10.1021/acssynbio.9b00230