{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:12:13Z","timestamp":1791547933827,"version":"4.3.4"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"7506","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2014,6]]},"DOI":"10.1038\/nature13423","type":"journal-article","created":{"date-parts":[[2014,6,18]],"date-time":"2014-06-18T11:37:04Z","timestamp":1403091424000},"page":"512-517","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":310,"title":["Structure of a modular polyketide synthase"],"prefix":"10.1038","volume":"510","author":[{"given":"Somnath","family":"Dutta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Whicher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi A.","family":"Hale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Chemler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grady R.","family":"Congdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison R. H.","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"H\u00e5kansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Sherman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Skiniotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,18]]},"reference":[{"key":"BFnature13423_CR1","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1021\/np200906s","volume":"75","author":"DJ Newman","year":"2012","unstructured":"Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 75, 311\u2013335 (2012)","journal-title":"J. Nat. Prod."},{"key":"BFnature13423_CR2","doi-asserted-by":"publisher","first-page":"3468","DOI":"10.1021\/cr0503097","volume":"106","author":"MA Fischbach","year":"2006","unstructured":"Fischbach, M. A. & Walsh, C. T. Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem. Rev. 106, 3468\u20133496 (2006)","journal-title":"Chem. Rev."},{"key":"BFnature13423_CR3","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1039\/b603600g","volume":"24","author":"S Smith","year":"2007","unstructured":"Smith, S. & Tsai, S. C. The type I fatty acid and polyketide synthases: a tale of two megasynthases. Nat. Prod. Rep. 24, 1041\u20131072 (2007)","journal-title":"Nat. Prod. Rep."},{"key":"BFnature13423_CR4","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S1074-5521(03)00156-X","volume":"10","author":"RW Broadhurst","year":"2003","unstructured":"Broadhurst, R. W., Nietlispach, D., Wheatcroft, M. P., Leadlay, P. F. & Weissman, K. J. The structure of docking domains in modular polyketide synthases. Chem. Biol. 10, 723\u2013731 (2003)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1021\/cb8002607","volume":"4","author":"TJ Buchholz","year":"2009","unstructured":"Buchholz, T. J. et al. Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains. ACS Chem. Biol. 4, 41\u201352 (2009)","journal-title":"ACS Chem. Biol."},{"key":"BFnature13423_CR6","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.chembiol.2007.07.012","volume":"14","author":"Y Tang","year":"2007","unstructured":"Tang, Y., Chen, A. Y., Kim, C. Y., Cane, D. E. & Khosla, C. Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem. Biol. 14, 931\u2013943 (2007)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR7","doi-asserted-by":"publisher","first-page":"11124","DOI":"10.1073\/pnas.0601924103","volume":"103","author":"Y Tang","year":"2006","unstructured":"Tang, Y., Kim, C. Y., Mathews, I. I., Cane, D. E. & Khosla, C. The 2.7-\u00c5 crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Proc. Natl Acad. Sci. USA 103, 11124\u201311129 (2006)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature13423_CR8","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jmb.2011.04.065","volume":"410","author":"J Zheng","year":"2011","unstructured":"Zheng, J. & Keatinge-Clay, A. T. Structural and functional analysis of C2-type ketoreductases from modular polyketide synthases. J. Mol. Biol. 410, 105\u2013117 (2011)","journal-title":"J. Mol. Biol."},{"key":"BFnature13423_CR9","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.str.2010.04.015","volume":"18","author":"J Zheng","year":"2010","unstructured":"Zheng, J., Taylor, C. A., Piasecki, S. K. & Keatinge-Clay, A. T. Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase. Structure 18, 913\u2013922 (2010)","journal-title":"Structure"},{"key":"BFnature13423_CR10","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.chembiol.2007.07.009","volume":"14","author":"AT Keatinge-Clay","year":"2007","unstructured":"Keatinge-Clay, A. T. A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem. Biol. 14, 898\u2013908 (2007)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR11","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.str.2006.01.009","volume":"14","author":"AT Keatinge-Clay","year":"2006","unstructured":"Keatinge-Clay, A. T. & Stroud, R. M. The structure of a ketoreductase determines the organization of the \u03b2-carbon processing enzymes of modular polyketide synthases. Structure 14, 737\u2013748 (2006)","journal-title":"Structure"},{"key":"BFnature13423_CR12","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.jmb.2008.09.084","volume":"384","author":"A Keatinge-Clay","year":"2008","unstructured":"Keatinge-Clay, A. Crystal structure of the erythromycin polyketide synthase dehydratase. J. Mol. Biol. 384, 941\u2013953 (2008)","journal-title":"J. Mol. Biol."},{"key":"BFnature13423_CR13","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.str.2009.10.018","volume":"18","author":"DL Akey","year":"2010","unstructured":"Akey, D. L. et al. Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway. Structure 18, 94\u2013105 (2010)","journal-title":"Structure"},{"key":"BFnature13423_CR14","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nchembio.964","volume":"8","author":"J Zheng","year":"2012","unstructured":"Zheng, J., Gay, D. C., Demeler, B., White, M. A. & Keatinge-Clay, A. T. Divergence of multimodular polyketide synthases revealed by a didomain structure. Nature Chem. Biol. 8, 615\u2013621 (2012)","journal-title":"Nature Chem. Biol."},{"key":"BFnature13423_CR15","doi-asserted-by":"publisher","first-page":"14445","DOI":"10.1074\/jbc.M110.214635","volume":"286","author":"JJ Gehret","year":"2011","unstructured":"Gehret, J. J. et al. Terminal alkene formation by the thioesterase of curacin A biosynthesis: structure of a decarboxylating thioesterase. J. Biol. Chem. 286, 14445\u201314454 (2011)","journal-title":"J. Biol. Chem."},{"key":"BFnature13423_CR16","doi-asserted-by":"publisher","first-page":"5726","DOI":"10.1002\/anie.201000032","volume":"49","author":"JB Scaglione","year":"2010","unstructured":"Scaglione, J. B. et al. Biochemical and structural characterization of the tautomycetin thioesterase: analysis of a stereoselective polyketide hydrolase. Angew. Chem. Int. Edn Engl. 49, 5726\u20135730 (2010)","journal-title":"Angew. Chem. Int. Edn Engl."},{"key":"BFnature13423_CR17","doi-asserted-by":"publisher","first-page":"12598","DOI":"10.1021\/bi0260177","volume":"41","author":"SC Tsai","year":"2002","unstructured":"Tsai, S. C., Lu, H., Cane, D. E., Khosla, C. & Stroud, R. M. Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases. Biochemistry 41, 12598\u201312606 (2002)","journal-title":"Biochemistry"},{"key":"BFnature13423_CR18","doi-asserted-by":"publisher","first-page":"14808","DOI":"10.1073\/pnas.011399198","volume":"98","author":"SC Tsai","year":"2001","unstructured":"Tsai, S. C. et al. Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. Proc. Natl Acad. Sci. USA 98, 14808\u201314813 (2001)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature13423_CR19","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.chembiol.2013.04.014","volume":"20","author":"SA Bonnett","year":"2013","unstructured":"Bonnett, S. A. et al. Structural and stereochemical analysis of a modular polyketide synthase ketoreductase domain required for the generation of a cis-alkene. Chem. Biol. 20, 772\u2013783 (2013)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR20","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1110\/ps.073011407","volume":"16","author":"VY Alekseyev","year":"2007","unstructured":"Alekseyev, V. Y., Liu, C. W., Cane, D. E., Puglisi, J. D. & Khosla, C. Solution structure and proposed domain\u2013domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Protein Sci. 16, 2093\u20132107 (2007)","journal-title":"Protein Sci."},{"key":"BFnature13423_CR21","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.chembiol.2013.09.015","volume":"20","author":"JR Whicher","year":"2013","unstructured":"Whicher, J. R. et al. Cyanobacterial polyketide synthase docking domains, a new tool for engineering natural product biosynthesis. Chem. Biol. 20, 1340\u20131351 (2013)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR22","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1126\/science.1161269","volume":"321","author":"T Maier","year":"2008","unstructured":"Maier, T., Leibundgut, M. & Ban, N. The crystal structure of a mammalian fatty acid synthase. Science 321, 1315\u20131322 (2008)","journal-title":"Science"},{"key":"BFnature13423_CR23","doi-asserted-by":"publisher","first-page":"12111","DOI":"10.1073\/pnas.95.21.12111","volume":"95","author":"Y Xue","year":"1998","unstructured":"Xue, Y., Zhao, L., Liu, H. W. & Sherman, D. H. A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity. Proc. Natl Acad. Sci. USA 95, 12111\u201312116 (1998)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature13423_CR24","doi-asserted-by":"publisher","first-page":"8441","DOI":"10.1021\/ja042592h","volume":"127","author":"CC Aldrich","year":"2005","unstructured":"Aldrich, C. C., Beck, B. J., Fecik, R. A. & Sherman, D. H. Biochemical investigation of pikromycin biosynthesis employing native penta- and hexaketide chain elongation intermediates. J. Am. Chem. Soc. 127, 8441\u20138452 (2005)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR25","doi-asserted-by":"publisher","first-page":"8910","DOI":"10.1021\/ja0504340","volume":"127","author":"CC Aldrich","year":"2005","unstructured":"Aldrich, C. C., Venkatraman, L., Sherman, D. H. & Fecik, R. A. Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide. J. Am. Chem. Soc. 127, 8910\u20138911 (2005)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR26","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nsmb.2497","volume":"20","author":"AM Lyon","year":"2013","unstructured":"Lyon, A. M., Dutta, S., Boguth, C. A., Skiniotis, G. & Tesmer, J. J. Full-length G\u03b1q\u2013phospholipase C-\u03b23 structure reveals interfaces of the C-terminal coiled-coil domain. Nature Struct. Mol. Biol. 20, 355\u2013362 (2013)","journal-title":"Nature Struct. Mol. Biol."},{"key":"BFnature13423_CR27","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1126\/science.1208245","volume":"333","author":"BS Strunk","year":"2011","unstructured":"Strunk, B. S. et al. Ribosome assembly factors prevent premature translation initiation by 40S assembly intermediates. Science 333, 1449\u20131453 (2011)","journal-title":"Science"},{"key":"BFnature13423_CR28","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/nsb0296-188","volume":"3","author":"J Staunton","year":"1996","unstructured":"Staunton, J. et al. Evidence for a double-helical structure for modular polyketide synthases. Nature Struct. Biol. 3, 188\u2013192 (1996)","journal-title":"Nature Struct. Biol."},{"key":"BFnature13423_CR29","doi-asserted-by":"publisher","first-page":"12363","DOI":"10.1021\/bi9616312","volume":"35","author":"CM Kao","year":"1996","unstructured":"Kao, C. M., Pieper, R., Cane, D. E. & Khosla, C. Evidence for two catalytically independent clusters of active sites in a functional modular polyketide synthase. Biochemistry 35, 12363\u201312368 (1996)","journal-title":"Biochemistry"},{"key":"BFnature13423_CR30","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1021\/bi971887n","volume":"37","author":"RS Gokhale","year":"1998","unstructured":"Gokhale, R. S., Lau, J., Cane, D. E. & Khosla, C. Functional orientation of the acyltransferase domain in a module of the erythromycin polyketide synthase. Biochemistry 37, 2524\u20132528 (1998)","journal-title":"Biochemistry"},{"key":"BFnature13423_CR31","doi-asserted-by":"publisher","unstructured":"Whicher, J. R. et al. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature \n                    http:\/\/dx.doi.org\/10.1038\/nature13409\n                    \n                   (this issue)","DOI":"10.1038\/nature13409"},{"key":"BFnature13423_CR32","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1021\/ja034574q","volume":"125","author":"Y Yin","year":"2003","unstructured":"Yin, Y., Lu, H., Khosla, C. & Cane, D. E. Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin\/methymycin polyketide synthase. J. Am. Chem. Soc. 125, 5671\u20135676 (2003)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR33","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1021\/bi300399u","volume":"51","author":"S Yuzawa","year":"2012","unstructured":"Yuzawa, S., Kapur, S., Cane, D. E. & Khosla, C. Role of a conserved arginine residue in linkers between the ketosynthase and acyltransferase domains of multimodular polyketide synthases. Biochemistry 51, 3708\u20133710 (2012)","journal-title":"Biochemistry"},{"key":"BFnature13423_CR34","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.chembiol.2007.07.013","volume":"14","author":"JD Kittendorf","year":"2007","unstructured":"Kittendorf, J. D., Beck, B. J., Buchholz, T. J., Seufert, W. & Sherman, D. H. Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. Chem. Biol. 14, 944\u2013954 (2007)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR35","doi-asserted-by":"publisher","first-page":"22066","DOI":"10.1073\/pnas.1014081107","volume":"107","author":"S Kapur","year":"2010","unstructured":"Kapur, S., Chen, A. Y., Cane, D. E. & Khosla, C. Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase. Proc. Natl Acad. Sci. USA 107, 22066\u201322071 (2010)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature13423_CR36","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1073\/pnas.1118734109","volume":"109","author":"S Kapur","year":"2012","unstructured":"Kapur, S. et al. Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation. Proc. Natl Acad. Sci. USA 109, 4110\u20134115 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature13423_CR37","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.chembiol.2011.07.016","volume":"18","author":"SA Bonnett","year":"2011","unstructured":"Bonnett, S. A. et al. Acyl-CoA subunit selectivity in the pikromycin polyketide synthase PikAIV: steady-state kinetics and active-site occupancy analysis by FTICR-MS. Chem. Biol. 18, 1075\u20131081 (2011)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR38","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1093\/emboj\/17.5.1183","volume":"17","author":"W Huang","year":"1998","unstructured":"Huang, W. et al. Crystal structure of \u03b2-ketoacyl-acyl carrier protein synthase II from E.  coli reveals the molecular architecture of condensing enzymes. EMBO J. 17, 1183\u20131191 (1998)","journal-title":"EMBO J."},{"key":"BFnature13423_CR39","doi-asserted-by":"publisher","first-page":"7359","DOI":"10.1021\/ja2112228","volume":"134","author":"JA Chemler","year":"2012","unstructured":"Chemler, J. A. et al. Biochemical and structural characterization of germicidin synthase: analysis of a type III polyketide synthase that employs acyl-ACP as a starter unit donor. J. Am. Chem. Soc. 134, 7359\u20137366 (2012)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR40","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/nsmb808","volume":"11","author":"AT Keatinge-Clay","year":"2004","unstructured":"Keatinge-Clay, A. T., Maltby, D. A., Medzihradszky, K. F., Khosla, C. & Stroud, R. M. An antibiotic factory caught in action. Nature Struct. Biol. 11, 888\u2013893 (2004)","journal-title":"Nature Struct. Biol."},{"key":"BFnature13423_CR41","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/11553","volume":"6","author":"JL Ferrer","year":"1999","unstructured":"Ferrer, J. L., Jez, J. M., Bowman, M. E., Dixon, R. A. & Noel, J. P. Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis. Nature Struct. Biol. 6, 775\u2013784 (1999)","journal-title":"Nature Struct. Biol."},{"key":"BFnature13423_CR42","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1126\/science.1138249","volume":"316","author":"M Leibundgut","year":"2007","unstructured":"Leibundgut, M., Jenni, S., Frick, C. & Ban, N. Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase. Science 316, 288\u2013290 (2007)","journal-title":"Science"},{"key":"BFnature13423_CR43","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S1074-5521(02)00146-1","volume":"9","author":"BJ Beck","year":"2002","unstructured":"Beck, B. J., Yoon, Y. J., Reynolds, K. A. & Sherman, D. H. The hidden steps of domain skipping: macrolactone ring size determination in the pikromycin modular polyketide synthase. Chem. Biol. 9, 575\u2013583 (2002)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR44","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/S1074-5521(01)00024-2","volume":"8","author":"CJ Rowe","year":"2001","unstructured":"Rowe, C. J. et al. Engineering a polyketide with a longer chain by insertion of an extra module into the erythromycin-producing polyketide synthase. Chem. Biol. 8, 475\u2013485 (2001)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR45","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1021\/cb400047s","volume":"8","author":"J Zheng","year":"2013","unstructured":"Zheng, J., Fage, C. D., Demeler, B., Hoffman, D. W. & Keatinge-Clay, A. T. The missing linker: a dimerization motif located within polyketide synthase modules. ACS Chem. Biol. 8, 1263\u20131270 (2013)","journal-title":"ACS Chem. Biol."},{"key":"BFnature13423_CR46","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.chembiol.2007.10.013","volume":"14","author":"G Bunkoczi","year":"2007","unstructured":"Bunkoczi, G. et al. Mechanism and substrate recognition of human holo ACP synthase. Chem. Biol. 14, 1243\u20131253 (2007)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR47","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/nature12679","volume":"505","author":"A Masoudi","year":"2014","unstructured":"Masoudi, A., Raetz, C. R., Zhou, P. & Pemble, C. W. IV Chasing acyl carrier protein through a catalytic cycle of lipid A production. Nature 505, 422\u2013426 (2014)","journal-title":"Nature"},{"key":"BFnature13423_CR48","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nature12810","volume":"505","author":"C Nguyen","year":"2014","unstructured":"Nguyen, C. et al. Trapping the dynamic acyl carrier protein in fatty acid biosynthesis. Nature 505, 427\u2013431 (2014)","journal-title":"Nature"},{"key":"BFnature13423_CR49","doi-asserted-by":"publisher","first-page":"6465","DOI":"10.1021\/ja010219t","volume":"123","author":"N Wu","year":"2001","unstructured":"Wu, N., Tsuji, S. Y., Cane, D. E. & Khosla, C. Assessing the balance between protein\u2013protein interactions and enzyme\u2013substrate interactions in the channeling of intermediates between polyketide synthase modules. J. Am. Chem. Soc. 123, 6465\u20136474 (2001)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR50","doi-asserted-by":"publisher","first-page":"4682","DOI":"10.1021\/ja029974c","volume":"125","author":"BJ Beck","year":"2003","unstructured":"Beck, B. J., Aldrich, C. C., Fecik, R. A., Reynolds, K. A. & Sherman, D. H. Iterative chain elongation by a pikromycin monomodular polyketide synthase. J. Am. Chem. Soc. 125, 4682\u20134683 (2003)","journal-title":"J. Am. Chem. Soc."},{"key":"BFnature13423_CR51","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1126\/science.1058092","volume":"291","author":"BA Pfeifer","year":"2001","unstructured":"Pfeifer, B. A., Admiraal, S. J., Gramajo, H., Cane, D. E. & Khosla, C. Biosynthesis of complex polyketides in a metabolically engineered strain of E.  coli. Science 291, 1790\u20131792 (2001)","journal-title":"Science"},{"key":"BFnature13423_CR52","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/S1074-5521(01)00047-3","volume":"8","author":"C S\u00e1nchez","year":"2001","unstructured":"S\u00e1nchez, C., Du, L., Edwards, D. J., Toney, M. D. & Shen, B. Cloning and characterization of a phosphopantetheinyl transferase from Streptomyces verticillus ATCC15003, the producer of the hybrid peptide\u2013polyketide antitumor drug bleomycin. Chem. Biol. 8, 725\u2013738 (2001)","journal-title":"Chem. Biol."},{"key":"BFnature13423_CR53","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1251\/bpo70","volume":"6","author":"M Ohi","year":"2004","unstructured":"Ohi, M., Li, Y., Cheng, Y. & Walz, T. Negative staining and image classification\u2014 powerful tools in modern electron microscopy. Biol. Proced. Online 6, 23\u201334 (2004)","journal-title":"Biol. Proced. Online"},{"key":"BFnature13423_CR54","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1006\/jsbi.1999.4174","volume":"128","author":"SJ Ludtke","year":"1999","unstructured":"Ludtke, S. J., Baldwin, P. R. & Chiu, W. EMAN: semiautomated software for high-resolution single-particle reconstructions. J. Struct. Biol. 128, 82\u201397 (1999)","journal-title":"J. Struct. Biol."},{"key":"BFnature13423_CR55","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","volume":"157","author":"G Tang","year":"2007","unstructured":"Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38\u201346 (2007)","journal-title":"J. Struct. Biol."},{"key":"BFnature13423_CR56","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1038\/nprot.2010.126","volume":"5","author":"ML Baker","year":"2010","unstructured":"Baker, M. L., Zhang, J., Ludtke, S. J. & Chiu, W. Cryo-EM of macromolecular assemblies at near-atomic resolution. Nature Protocols 5, 1697\u20131708 (2010)","journal-title":"Nature Protocols"},{"key":"BFnature13423_CR57","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.jmb.2003.07.013","volume":"333","author":"PB Rosenthal","year":"2003","unstructured":"Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721\u2013745 (2003)","journal-title":"J. Mol. Biol."},{"key":"BFnature13423_CR58","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jsb.2008.05.010","volume":"164","author":"JJ Fern\u00e1ndez","year":"2008","unstructured":"Fern\u00e1ndez, J. J., Luque, D., Caston, J. R. & Carrascosa, J. L. Sharpening high resolution information in single particle electron cryomicroscopy. J. Struct. Biol. 164, 170\u2013175 (2008)","journal-title":"J. Struct. Biol."},{"key":"BFnature13423_CR59","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nmeth.2115","volume":"9","author":"SH Scheres","year":"2012","unstructured":"Scheres, S. H. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nature Methods 9, 853\u2013854 (2012)","journal-title":"Nature Methods"},{"key":"BFnature13423_CR60","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nmeth.2472","volume":"10","author":"X Li","year":"2013","unstructured":"Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10, 584\u2013590 (2013)","journal-title":"Nature Methods"},{"key":"BFnature13423_CR61","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","volume":"135","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24\u201335 (2013)","journal-title":"Ultramicroscopy"},{"key":"BFnature13423_CR62","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.jmb.2011.09.008","volume":"413","author":"R Henderson","year":"2011","unstructured":"Henderson, R. et al. Tilt-pair analysis of images from a range of different specimens in single-particle electron cryomicroscopy. J. Mol. Biol. 413, 1028\u20131046 (2011)","journal-title":"J. Mol. Biol."},{"key":"BFnature13423_CR63","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/j.str.2013.04.016","volume":"21","author":"SC Murray","year":"2013","unstructured":"Murray, S. C., Flanagan, J., Popova, O. B., Chiu, W., Ludtke, S. J. & Serysheva, I. I. Validation of cryo-EM structure of IP3R1 channel. Structure 21, 900\u2013909 (2013)","journal-title":"Structure"},{"key":"BFnature13423_CR64","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2014a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004)","journal-title":"J. Comput. Chem."},{"key":"BFnature13423_CR65","doi-asserted-by":"publisher","first-page":"11232","DOI":"10.1021\/ja404134f","volume":"135","author":"DA Hansen","year":"2013","unstructured":"Hansen, D. A. et al. Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin. J. Am. Chem. Soc. 135, 11232\u201311238 (2013","journal-title":"J. Am. Chem. Soc."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature13423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13423","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:21:54Z","timestamp":1684419714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature13423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":65,"journal-issue":{"issue":"7506","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["BFnature13423"],"URL":"https:\/\/doi.org\/10.1038\/nature13423","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718462923.793514547","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718462923.793496650","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718462923.793504811","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718462923.793497701","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718462923.793496522","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718462923.793497896","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6]]},"assertion":[{"value":"7 May 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}