Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs
Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs
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DOI：
10.1021/acs.orglett.1c04089
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发表时间：
2021-12-23
期刊：
影响因子：
5.2
通讯作者：
Morita, Hiroyuki
中科院分区：
文献类型：
--
作者：
Lee, Yuan-E;Nakashima, Yu;Morita, Hiroyuki
Delta(9)-四氢大麻酚（Delta(9)-THC）的治疗效果可以通过修饰C-3上的戊基片段来增强。在生物合成Delta(9)-THC过程中，分别以F24I取代的大麻油酸环化酶和L190G取代的四肽合成酶的工程，为再环酸生成6-十一烷基再环酸提供了平台。这些结果为在C-3上具有不同化学酰基基团的四氢大麻酚类似物的开发提供了见解。
The therapeutic effects of Delta(9)-tetrahydrocannabinol (Delta(9)-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 Delta(9)-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.