Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production

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

doi:10.1021/acssynbio.9b00230

Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production

Journal Article · Wed Sep 18 00:00:00 EDT 2019 · ACS Synthetic Biology

DOI:https://doi.org/10.1021/acssynbio.9b00230· OSTI ID:1594932

Eiben, Christopher B. ^[1]; de Rond, Tristan ^[2]; Bloszies, Clayton ^[3]; Gin, Jennifer ^[4]; Chiniquy, Jennifer ^[4]; Baidoo, Edward E. K. ^[4]; ^[4]; ^[4]; ^[5]; ^[6]

Univ. of California, San Francisco, CA (United States)
Scripps Center for Mass Spectrometry and Metabolomics, San Diego, CA (United States); Univ. of California, San Francisco, CA (United States)
Univ. of California, Davis, CA (United States). National Inst. of Health West Coast Metabolomics Center
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Dept. of Energy Agile BioFoundry, Emeryville, CA (United States)
Univ. of California, Davis, CA (United States)
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Technical Univ. of Denmark, Roskilde (Denmark). Hørsholm; Shenzhen Inst. for Advanced Technologies, Shenzhen (China)

The 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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1594932

Journal Information:: ACS Synthetic Biology, Journal Name: ACS Synthetic Biology Journal Issue: 10 Vol. 8; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
HDMAPP
HIPP
homodimethylallyl pyrophosphate
homoisopentenyl pyrophosphate
juvenile hormones
mevalonate pathway
terpenes

Mevalonate Pathway Promiscuity Enables Noncanonical Terpene Production

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References (52)

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