Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs

Yuan-E Lee; Yu Nakashima; Takeshi Kodama; Xinrui Chen; Hiroyuki Morita

doi:10.1021/acs.orglett.1c04089

Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs

Org Lett. 2022 Jan 14;24(1):410-414. doi: 10.1021/acs.orglett.1c04089. Epub 2021 Dec 23.

Authors

Yuan-E Lee¹, Yu Nakashima¹, Takeshi Kodama¹, Xinrui Chen¹, Hiroyuki Morita¹

Affiliation

¹ Institute of Natural Medicine, University of Toyama, Toyoma 930-0194, Japan.

PMID: 34939812
DOI: 10.1021/acs.orglett.1c04089

Abstract

The therapeutic effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) can be enhanced by modifications of the pentyl moiety at C-3. The engineering of Cannabis sativa olivetolic acid cyclase and tetraketide synthase with F24I and L190G substitutions, respectively, in the biosynthesis of Δ⁹-THC serves as a platform for the generation of resorcylic acids up to 6-undecylresorcylic acid. These results provide insights into the development of THC analogs with chemically distinct acyl moieties at C-3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Salicylates*

Substances

Salicylates
olivetolic acid