A cell-free platform for the prenylation of natural products and application to cannabinoid production

Valliere, Meaghan A.; Korman, Tyler P.; Woodall, Nicholas B.; Khitrov, Gregory A.; Taylor, Robert E.; Baker, David; Bowie, James U.

doi:10.1038/s41467-019-08448-y

A cell-free platform for the prenylation of natural products and application to cannabinoid production

Journal Article · Mon Feb 04 00:00:00 EST 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-08448-y· OSTI ID:1613646

Valliere, Meaghan A. ^[1]; Korman, Tyler P. ^[2]; Woodall, Nicholas B. ^[3]; Khitrov, Gregory A. ^[2]; Taylor, Robert E. ^[2]; ^[3]; Bowie, James U. ^[2]

Univ. of California, Los Angeles, CA (United States); DOE/OSTI
Univ. of California, Los Angeles, CA (United States)
Univ. of Washington, Seattle, WA (United States)

Prenylation of natural compounds adds structural diversity, alters biological activity, and enhances therapeutic potential. Because prenylated compounds often have a low natural abundance, alternative production methods are needed. Metabolic engineering enables natural product biosynthesis from inexpensive biomass, but is limited by the complexity of secondary metabolite pathways, intermediate and product toxicities, and substrate accessibility. Alternatively, enzyme catalyzed prenyl transfer provides excellent regio- and stereo-specificity, but requires expensive isoprenyl pyrophosphate substrates. Here we develop a flexible cell-free enzymatic prenylating system that generates isoprenyl pyrophosphate substrates from glucose to prenylate an array of natural products. The system provides an efficient route to cannabinoid precursors cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA) at >1 g/L, and a single enzymatic step converts the precursors into cannabidiolic acid (CBDA) and cannabidivarinic acid (CBDVA). Cell-free methods may provide a powerful alternative to metabolic engineering for chemicals that are hard to produce in living organisms.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Advanced Research Projects Agency - Energy (ARPA-E)

Grant/Contract Number:: AR0000556; FC02-02ER63421

OSTI ID:: 1613646

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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