{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T18:52:15Z","timestamp":1772909535066,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM124112"],"award-info":[{"award-number":["GM124112"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enzymatic platforms for producing malonyl\u2010CoA\u2010based extender units required for polyketide biosynthesis are often based on malonyl\u2010CoA ligases such as MatB from <jats:italic>Rhizobium trifolii<\/jats:italic> and <jats:italic>Rhodopseudomonas palustris<\/jats:italic>. However, despite broad interest in the fluorination of polyketides and prior success with engineering MatB homologs, the suitability of MatB for accessing the tertiary substituted fluoromethylmalonyl\u2010CoA needed to produce flurithromycin and solithromycin has not yet been reported. Herein, we report the structure\u2010guided engineering of a MatB homolog to optimize the production of fluoromethylmalonyl\u2010CoA, resulting in a variant with increased conversion and providing a platform to produce a suitable building block mixture for fluorinated macrolide production. Additionally, the mutant demonstrated broad utility for various substituted malonyl\u2010CoAs. The MatB mutant sets the stage to access fluorinated macrolides by coupling it with altered PKS machinery to install fluorinated malonyl\u2010CoA into macrolide scaffolds.<\/jats:p>","DOI":"10.1002\/cbic.202400532","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T10:59:10Z","timestamp":1721645950000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineering of a Malonyl\u2010CoA Ligase for Production of Fluorinated Polyketide Extender Units"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-120X","authenticated-orcid":false,"given":"Thaddeus Q.","family":"Paulsel","sequence":"first","affiliation":[{"name":"Department of Chemistry NC State University  2620 Yarbrough Drive Raleigh NC 27607 USA"},{"name":"Comparative Medicine Institute NC State University  1001 William Moore Drive Raleigh NC 27606 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-9063","authenticated-orcid":false,"given":"Gavin J.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Chemistry NC State University  2620 Yarbrough Drive Raleigh NC 27607 USA"},{"name":"Comparative Medicine Institute NC State University  1001 William Moore Drive Raleigh NC 27606 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-018-2021-9"},{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"T.\u2005Q. Paulsel G.\u2005J. Williams ChemBioChem2023 24 e202300386 DOI:10.1002\/cbic.202300386.","DOI":"10.1002\/cbic.202300386"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0028368"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201100383"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3ob40633d"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.2c00425"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01733-12"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201706696"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.checat.2022.09.042"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.12.014"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/lam.13039"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.08.035"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01962180"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"A. Rittner M. Joppe J.\u2005J. Schmidt L.\u2005M. Mayer S. Reiners E. Heid D. Herzberg D.\u2005H. Sherman M. Grininger Nat. Chem.2022 14 1000\u20131006 DOI:10.1038\/s41557-022-00996-z.","DOI":"10.1038\/s41557-022-00996-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb3003489"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3ob40633d"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b10521"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00341"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22497-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","unstructured":"M.\u2005C. Walker B.\u2005W. Thuronyi L.\u2005K. Charkoudian B. Lowry C. Khosla M.\u2005C.\u2005Y. Chang Science (1979)2013 341 1089-1094 DOI:10.1126\/science.1242345.","DOI":"10.1126\/science.1242345"},{"key":"e_1_2_9_21_1","unstructured":"I. Koryakina Synthetic Biology Approaches for Combinatorial Biosynthesis of Polyketide Natural Products. Dissertation North Carolina State University 2014."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01070-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-022-00996-z"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c11027"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","unstructured":"S. Sirirungruang O. Ad T.\u2005M. Privalsky S. Ramesh J.\u2005L. Sax H. Dong E.\u2005E.\u2005K. Baidoo B. Amer C. Khosla M.\u2005C.\u2005Y. Chang Nat. Chem. Biol.2022 18 886\u2013893 DOI:10.1038\/s41589-022-01070-y.","DOI":"10.1038\/s41589-022-01070-y"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","unstructured":"B. Spingler C. 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