Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

Simple item page
dc.citation.firstpage730en_US
dc.citation.journalTitleNature Chemical Biologyen_US
dc.citation.lastpage737en_US
dc.citation.volumeNumber14en_US
dc.contributor.authorWang, Nan L.en_US
dc.contributor.authorRudolf, Jeffrey D.en_US
dc.contributor.authorDong, Liao-Binen_US
dc.contributor.authorOsipiuk, Jerzyen_US
dc.contributor.authorHatzos-Skintges, Catherineen_US
dc.contributor.authorEndres, Michaelen_US
dc.contributor.authorChang, Chin-Yuanen_US
dc.contributor.authorBabnigg, Gyorgyen_US
dc.contributor.authorJoachimiak, Andrzejen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorShen, Benen_US
dc.date.accessioned2019-11-22T16:19:58Zen_US
dc.date.available2019-11-22T16:19:58Zen_US
dc.date.issued2018en_US
dc.description.abstractAcyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology.en_US
dc.identifier.citationWang, Nan L., Rudolf, Jeffrey D., Dong, Liao-Bin, et al.. "Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme." <i>Nature Chemical Biology,</i> 14, (2018) Springer Nature: 730-737. https://doi.org/10.1038/s41589-018-0061-0.en_US
dc.identifier.digitalnihms952907en_US
dc.identifier.doihttps://doi.org/10.1038/s41589-018-0061-0en_US
dc.identifier.urihttps://hdl.handle.net/1911/107723en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Natureen_US
dc.titleNatural separation of the acyl-CoA ligase reaction results in a non-adenylating enzymeen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
nihms952907.pdf
Size:
903.06 KB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
BioSciences Publications