AI Article Synopsis
- - This study identifies a new type of acyl-CoA ligase called PtmA2, which can catalyze the thioesterification process without the usual adenylation step, contradicting previous beliefs about how these enzymes function.
- - Researchers found that both PtmA1 and PtmA2 are essential for the complete activation of CoA in the biosynthesis of platensimycin and platencin; inhibiting these genes led to the buildup of specific intermediates.
- - Detailed analysis of PtmA2 showed it can bind to both free acid and adenylate substrates, and experiments revealed that it undergoes a domain alternation mechanism, providing insights into how separated acyl-CoA lig
Article Abstract
Acyl-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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008203 | PMC |
| http://dx.doi.org/10.1038/s41589-018-0061-0 | DOI Listing |
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