| Structural highlights
7w6g is a 4 chain structure with sequence from Cannabis sativa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.1Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
OLIS_CANSA Polyketide synthase responsible for olivetol biosynthesis. Catalyzes the first step in the cannabinoids biosynthetic pathway. The preferred substrate is hexanoyl-CoA, but accepts also CoA esters with C4 to C8 aliphatic side chains. When using malonyl-CoA and hexanoyl-CoA as substrates, produces undetermined compounds distinct form olivetol or olivetolic acid (PubMed:19581347) that could be hexanoyl triacetic acid lactone (HTAL) (PubMed:18323613) and pentyl diacetic acid lactone (PDAL) (PubMed:22802619). Produces olivetolic acid when acting in concert with olivetolic acid cyclase (OAC).[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs.,Lee YE, Nakashima Y, Kodama T, Chen X, Morita H Org Lett. 2022 Jan 14;24(1):410-414. doi: 10.1021/acs.orglett.1c04089. Epub 2021 , Dec 23. PMID:34939812[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Taguchi C, Taura F, Tamada T, Shoyama Y, Shoyama Y, Tanaka H, Kuroki R, Morimoto S. Crystallization and preliminary X-ray diffraction studies of polyketide synthase-1 (PKS-1) from Cannabis sativa. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Mar 1;64(Pt 3):217-20., doi: 10.1107/S1744309108003795. Epub 2008 Feb 29. PMID:18323613 doi:http://dx.doi.org/10.1107/S1744309108003795
- ↑ Taura F, Tanaka S, Taguchi C, Fukamizu T, Tanaka H, Shoyama Y, Morimoto S. Characterization of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway. FEBS Lett. 2009 Jun 18;583(12):2061-6. doi: 10.1016/j.febslet.2009.05.024. Epub, 2009 May 19. PMID:19454282 doi:http://dx.doi.org/10.1016/j.febslet.2009.05.024
- ↑ Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA. Identification of candidate genes affecting Delta9-tetrahydrocannabinol biosynthesis in Cannabis sativa. J Exp Bot. 2009;60(13):3715-26. doi: 10.1093/jxb/erp210. Epub 2009 Jul 6. PMID:19581347 doi:http://dx.doi.org/10.1093/jxb/erp210
- ↑ Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12811-6. doi:, 10.1073/pnas.1200330109. Epub 2012 Jul 16. PMID:22802619 doi:http://dx.doi.org/10.1073/pnas.1200330109
- ↑ Lee YE, Nakashima Y, Kodama T, Chen X, Morita H. 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. PMID:34939812 doi:10.1021/acs.orglett.1c04089
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