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Publication Abstract from PubMed

Ketosynthase-like decarboxylase (KS(Q)) domains are widely distributed in the loading modules of modular type I polyketide synthases (PKSs) and catalyze the decarboxylation of the (alkyl-)malonyl unit bound to the acyl carrier protein (ACP) in the loading module for the construction of the PKS starter unit. Previously, we performed a structural and functional analysis of the GfsA KS(Q) domain involved in the biosynthesis of macrolide antibiotic FD-891. We furthermore revealed the recognition mechanism for the malonic acid thioester moiety of the malonyl-GfsA loading module ACP (ACP(L)) as a substrate. However, the exact recognition mechanism for the GfsA ACP(L) moiety remains unclear. Here, we present a structural basis for the interactions between the GfsA KS(Q) domain and GfsA ACP(L). We determined the crystal structure of the GfsA KS(Q)-acyltransferase (AT) didomain in complex with ACP(L) (ACP(L)=KS(Q)AT complex) by using a pantetheine crosslinking probe. We identified the key amino acid residues involved in the KS(Q) domain-ACP(L) interactions and confirmed the importance of these residues by mutational analysis. The binding mode of ACP(L) to the GfsA KS(Q) domain is similar to that of ACP to the ketosynthase domain in modular type I PKSs. Furthermore, comparing the ACP(L)=KS(Q)AT complex structure with other full-length PKS module structures provides important insights into the overall architectures and conformational dynamics of the type I PKS modules.

Structure-Based Analysis of Transient Interactions between Ketosynthase-like Decarboxylase and Acyl Carrier Protein in a Loading Module of Modular Polyketide Synthase.,Chisuga T, Murakami S, Miyanaga A, Kudo F, Eguchi T ACS Chem Biol. 2023 May 22. doi: 10.1021/acschembio.3c00151. PMID:37216195^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.