{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T19:48:21Z","timestamp":1773431301522,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tautomycetin (TMC) is a linear polyketide metabolite produced by Streptomyces sp. CK4412 that has been reported to possess multiple biological functions including T cell-specific immunosuppressive and anticancer activities that occur through a mechanism of differential inhibition of protein phosphatases such as PP1, PP2A, and SHP2. We previously reported the characterization of the entire TMC biosynthetic gene cluster constituted by multifunctional type I polyketide synthase (PKS) assembly and suggested that the linear form of TMC could be generated via free acid chain termination by a narrow TMC thioesterase (TE) pocket. The modular nature of the assembly presents a unique opportunity to alter or interchange the native biosynthetic domains to produce targeted variants of TMC. Herein, we report swapping of the TMC TE domain sequence with the exact counterpart of the macrocyclic polyketide pikromycin (PIK) TE. PIK TE-swapped Streptomyces sp. CK4412 mutant produced not only TMC, but also a cyclized form of TMC, implying that the bioengineering based in vivo custom construct can be exploited to produce engineered macrolactones with new structural functionality.<\/jats:p>","DOI":"10.1007\/s10295-016-1790-2","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T03:49:23Z","timestamp":1465444163000},"page":"1189-1193","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in <i>Streptomyces<\/i> sp. CK4412"],"prefix":"10.1093","volume":"43","author":[{"given":"Ashootosh","family":"Tripathi","sequence":"first","affiliation":[{"name":"grid.214458.e 0000000086837370 Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry, and Microbiology and Immunology University of Michigan 48109-2216 Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Sun","family":"Choi","sequence":"additional","affiliation":[{"name":"grid.202119.9 0000000123648385 Department of Biological Engineering Inha University 402-751 Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H","family":"Sherman","sequence":"additional","affiliation":[{"name":"grid.214458.e 0000000086837370 Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry, and Microbiology and Immunology University of Michigan 48109-2216 Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eung-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"grid.202119.9 0000000123648385 Department of Biological Engineering Inha University 402-751 Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,8,1]]},"reference":[{"issue":"12","key":"2021033110565144200_CR1","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/S1074-5521(00)00039-9","article-title":"Mechanisms of molecular recognition in the pikromycin polyketide synthase","volume":"7","author":"Chen","year":"2000","journal-title":"Chem Biol"},{"key":"2021033110565144200_CR2","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1099\/mic.0.2006\/003194-0","article-title":"Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. 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