Structural highlights
FunctionPublication Abstract from PubMedIn the biosynthesis of the macrolactam antibiotic cremimycin, the 3-aminononanoic acid starter unit is formed via a non-2-enoyl acyl carrier protein thioester intermediate, which is presumed to be constructed by cis-acyltransferase (AT) polyketide synthases (PKSs) CmiP2, CmiP3, and CmiP4. While canonical cis-AT PKS modules are comprised of a single polypeptide, the PKS module formed by CmiP2 and CmiP3 is split within the dehydratase (DH) domain. Here, we report the enzymatic function and the structural features of this split-DH domain. In vitro analysis showed that the split-DH domain catalyzes the dehydration reaction of (R)-3-hydroxynonanoyl N-acetylcysteamine thioester (SNAC) to form (E)-non-2-enoyl-SNAC, suggesting that the split-DH domain is catalytically active in cremimycin biosynthesis. In addition, structural analysis revealed that the CmiP2 and CmiP3 subunits of the split-DH domain form a tightly associated heterodimer through several hydrogen bonding and hydrophobic interactions, which are similar to those of canonical DH domains of other cis-AT PKSs. These results indicate that the split-DH domain has the same function and structure as common cis-AT PKS DH domains. Functional and Structural Analyses of the Split-Dehydratase Domain in the Biosynthesis of Macrolactam Polyketide Cremimycin.,Kawasaki D, Miyanaga A, Chisuga T, Kudo F, Eguchi T Biochemistry. 2019 Nov 18. doi: 10.1021/acs.biochem.9b00897. PMID:31721563[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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