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

Yuan E. Lee, Yu Nakashima, Takeshi Kodama, Xinrui Chen, Hiroyuki Morita^*

^*Corresponding author for this work

Section of Natural Products & Drug Discovery, Division of Medicinal Resources, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Pages (from-to)	410-414
Number of pages	5
Journal	Organic Letters
Volume	24
Issue number	1
DOIs	https://doi.org/10.1021/acs.orglett.1c04089
State	Published - 2022/01/14

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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

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.",

author = "Lee, {Yuan E.} and Yu Nakashima and Takeshi Kodama and Xinrui Chen and Hiroyuki Morita",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society",

year = "2022",

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doi = "10.1021/acs.orglett.1c04089",

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T1 - Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs

AU - Lee, Yuan E.

AU - Nakashima, Yu

AU - Kodama, Takeshi

AU - Chen, Xinrui

AU - Morita, Hiroyuki

PY - 2022/1/14

Y1 - 2022/1/14

N2 - 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.

AB - 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.

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SN - 1523-7060

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JO - Organic Letters

JF - Organic Letters

IS - 1

ER -

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

Abstract

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