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Publication Abstract from PubMed

Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in the biosynthesis of various polyketide natural products. The trans-AT modular polyketide synthases have a discrete trans-acting AT for the loading of an acyl unit onto the acyl carrier protein (ACP) located within each module. Despite the importance of protein-protein interactions between ATs and ACPs in trans-AT assembly lines, the dynamic actions of ACPs and trans-acting ATs remain largely uncharacterized because of the inherently transient nature of ACP-enzyme interactions. Herein, we report the crystal structure of the AT-ACP complex of disorazole trans-AT polyketide synthase. We used a bromoacetamide pantetheine cross-linking probe in combination with a Cys mutation to trap the transient AT-ACP complex, allowing the determination of the crystal structure of the disorazole AT-ACP complex at 2.03 A resolution. On the basis of the cross-linked AT-ACP complex structure, ACP residues recognized by trans-acting AT were identified and validated by mutational studies, which demonstrated that the disorazole AT recognizes the loop 1 and helix III' residues of disorazole ACP. The disorazole AT-ACP complex structure presents a foundation for defining the dynamic processes associated with trans-acting ATs and provides detailed mechanistic insights into their ability to recognize ACPs.

Structural Basis of Protein-Protein Interactions between a trans-Acting Acyltransferase and Acyl Carrier Protein in Polyketide Disorazole Biosynthesis.,Miyanaga A, Ouchi R, Ishikawa F, Goto E, Tanabe G, Kudo F, Eguchi T J Am Chem Soc. 2018 Jun 13. doi: 10.1021/jacs.8b04162. PMID:29870659^[1]

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