{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:50:10Z","timestamp":1787014210276,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T00:00:00Z","timestamp":1454371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008695","name":"Japan Foundation for Applied Enzymology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2016,3]]},"abstract":"\n \n \n In polyketide biosynthesis, ring formation is one of the key diversification steps. Olivetolic acid cyclase (\n OAC<\/jats:styled-content>\n ) from\n Cannabis sativa,<\/jats:italic>\n involved in cannabinoid biosynthesis, is the only known plant polyketide cyclase. In addition, it is the only functionally characterized plant \u03b1+\u03b2 barrel (\n DABB<\/jats:styled-content>\n ) protein that catalyzes the C2\u2013C7 aldol cyclization of the linear pentyl tetra\u2010\u03b2\u2010ketide CoA as the substrate, to generate olivetolic acid (\n OA<\/jats:styled-content>\n ). Herein, we solved the\n OAC<\/jats:styled-content>\n apo and\n OAC<\/jats:styled-content>\n \u2013\n OA<\/jats:styled-content>\n complex binary crystal structures at 1.32 and 1.70 \u00c5 resolutions, respectively. The crystal structures revealed that the enzyme indeed belongs to the\n DABB<\/jats:styled-content>\n superfamily, as previously proposed, and possesses a unique active\u2010site cavity containing the pentyl\u2010binding hydrophobic pocket and the polyketide binding site, which have never been observed among the functionally and structurally characterized bacterial polyketide cyclases. Furthermore, site\u2010directed mutagenesis studies indicated that Tyr72 and His78 function as acid\/base catalysts at the catalytic center. Structural and\/or functional studies of\n OAC<\/jats:styled-content>\n suggested that the enzyme lacks thioesterase and aromatase activities. These observations demonstrated that\n OAC<\/jats:styled-content>\n employs unique catalytic machinery utilizing acid\/base catalytic chemistry for the formation of the precursor of\n OA<\/jats:styled-content>\n . The structural and functional insights obtained in this work thus provide the foundation for analyses of the plant polyketide cyclases that will be discovered in the future.\n <\/jats:p>\n <\/jats:sec>\n \n Data deposition<\/jats:title>\n \n Structural data reported in this paper are available in the Protein Data Bank under the accession numbers\n 5B08<\/jats:ext-link>\n for the\n OAC<\/jats:styled-content>\n apo,\n 5B09<\/jats:ext-link>\n for the\n OAC<\/jats:styled-content>\n \u2013\n OA<\/jats:styled-content>\n binary complex and\n 5B0A<\/jats:ext-link>\n ,\n 5B0B<\/jats:ext-link>\n ,\n 5B0C<\/jats:ext-link>\n ,\n 5B0D<\/jats:ext-link>\n ,\n 5B0E<\/jats:ext-link>\n ,\n 5B0F<\/jats:ext-link>\n and\n 5B0G<\/jats:ext-link>\n for the\n OAC<\/jats:styled-content>\n His5Q, Ile7F, Tyr27F, Tyr27W, Val59M, Tyr72F and His78S mutant enzymes, respectively.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/febs.13654","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T21:56:45Z","timestamp":1453154205000},"page":"1088-1106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Structural basis for olivetolic acid formation by a polyketide cyclase from\n Cannabis sativa<\/i>"],"prefix":"10.1111","volume":"283","author":[{"given":"Xinmei","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Natural Medicine University of Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsui","sequence":"additional","affiliation":[{"name":"Institute of Natural Medicine University of Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kodama","sequence":"additional","affiliation":[{"name":"Institute of Natural Medicine University of Toyama 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