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CMB\u2010M0232, are the newest members of this structural class. Here, the biosynthetic pathway for nocardiopsins A\u2013D (<jats:bold>4<\/jats:bold>\u2013<jats:bold>7<\/jats:bold>) is revealed by cloning, sequencing, and bioinformatic analyses of the <jats:italic>nsn<\/jats:italic> gene cluster. In vitro evaluation of recombinant NsnL revealed that this lysine cyclodeaminase catalyzes the conversion of <jats:sc>L<\/jats:sc>\u2010lysine into the <jats:sc>L<\/jats:sc>\u2010pipecolic acid incorporated into <jats:bold>4<\/jats:bold> and <jats:bold>5<\/jats:bold>. Bioinformatic analyses supported the conjecture that a linear nocardiopsin precursor is equipped with the hydroxy group required for macrolide closure in a previously unobserved manner by employing a P450 epoxidase (NsnF) and limonene epoxide hydrolase homologue (NsnG). The <jats:italic>nsn<\/jats:italic> cluster also encodes candidates for tetrahydrofuran group biosynthesis. The nocardiopsin pathway provides opportunities for engineering of FKBP\u2010binding metabolites and for probing new enzymology in nature's polyketide tailoring arsenal.<\/jats:p>","DOI":"10.1002\/cbic.201500007","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T15:41:26Z","timestamp":1425570086000},"page":"990-997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of the Nocardiopsin Biosynthetic Gene Cluster Reveals Similarities to and Differences from the Rapamycin and FK\u2010506 Pathways"],"prefix":"10.1002","volume":"16","author":[{"given":"Dana M.","family":"Bis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang H.","family":"Ban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elle D.","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norah","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,5]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.727"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.1249"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(94)02425-B"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1039\/b804602f"},{"key":"e_1_2_6_5_2","unstructured":"\u00a0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200902933"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2012.10.104"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1012"},{"key":"e_1_2_6_9_2","unstructured":"\u00a0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr030107f"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/B301028G"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.7839"},{"key":"e_1_2_6_13_2","unstructured":"\u00a0"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(09)04808-3"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg607"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062136"},{"key":"e_1_2_6_17_2","unstructured":"\u00a0"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00526.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi050230w"},{"key":"e_1_2_6_20_2","unstructured":"\u00a0"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.29176-0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2006.03.021"},{"key":"e_1_2_6_23_2","unstructured":"\u00a0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.19.5052-5057.1998"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg275"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja050940p"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337542100"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01442-10"},{"key":"e_1_2_6_29_2","unstructured":"\u00a0"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201404977"},{"key":"e_1_2_6_30_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201404977"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.119"},{"key":"e_1_2_6_32_2","unstructured":"\u00a0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019077108"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0mt00081g"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja046104h"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.48.92"},{"key":"e_1_2_6_37_2","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1128\/AAC.43.7.1662","volume":"43","author":"Woo A. 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