Binding and pKa Modulation of a Polycyclic Substrate Analogue in a Type II Polyketide Acyl Carrier Protein
Year: 2011
Type: article
Abstract: Type II polyketide synthases are biosynthetic enzymatic pathways responsible for the production of complex aromatic natural products with important biological activities. In these systems, biosynthetic intermediates are covalently bound to a small acyl carrier protein that associates with the synthase enzymes and delivers the bound intermediate to each active site. In the closely related fatty acid synthases of bacteria and plants, the acyl carrier protein acts to sequester and protect attached intermediates within its helices. Here we investigate the type II polyketide synthase acyl carrier protein from the actinorhodin biosynthetic pathway and demonstrate its ability to internalize the tricyclic, polar molecule emodic acid. Elucidating the interaction of acyl carrier proteins with bound analogues resembling late-stage intermediates in the actinorhodin pathway could prove valuable in efforts to engineer these systems toward rational design and biosynthesis of novel compounds.
Source: ACS Chemical Biology
DOI: 10.1021/cb200004k
Authors: Robert W. Haushalter, Fabian V. Filipp, Kwang-seuk Ko, Ricky Yu, Stanley J. Opella, Michael D. Burkart
Institution: University of California San Diego
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Proteomic methodologies for polyketide biosynthesis (RMI), The Molecular Basis of Regio-Specificity in Fungal Polyketide Synthase, G1761472676, G3138544804, Tumor pyruvate kinase as key regulator of cancer metabolism, Site Specific Protein Labeling In Vivo Through Genetically Engineered Phosphopant
OpenAlex ID: W2046666269