| Title | Acyltransferase Mediated Polyketide Release from a Fungal Megasynthase. | | Author(s) | Xie X, Meehan MJ, Xu W, Dorrestein PC, Tang Y | | Institution | Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, and Skaggs School of Pharmacy and Pharmaceutical Sciences and Departments of Pharmacology, Chemistry and Biochemistry, University of California, San Diego, California 92093. | | Source | J Am Chem Soc 2009 Jun 24; 131(24):8388-8389. | | Abstract | LovF is a highly reducing polyketide synthase (HR-PKS) from the filamentous fungus Aspergillus terreus. LovF synthesizes the alpha-S-methylbutyrate side chain that is subsequently transferred to monacolin J to yield the cholesterol-lowering natural product lovastatin. In the report, we expressed the full length LovF and reconstituted the megasynthase activities in vitro. We confirmed the diketide product of LovF is offloaded from the LovF ACP domain by the dissociated acyltransferase LovD. This represents the first example of acyltransferase-mediated release of polyketide products from fungal PKSs. We determined LovD primarily interacts with the ACP domain of LovF and the protein-protein interactions lead to highly efficient transfer of the diketide product. The catalytic efficiency is enhanced nearly 1 x 10(6)-fold when LovF was used as the acyl carrier instead of N-acetylcysteamine. Reconstitution and characterization of the LovF offloading mechanism provide new insights into the functions of fungal HR-PKS. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19530726 |
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