1tqy

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1tqy, resolution 2.00Å

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The Actinorhodin Ketosynthase/Chain Length Factor

Overview

The synthesis of aromatic polyketides, such as actinorhodin, tetracycline and doxorubicin, begins with the formation of a polyketide chain. In type II polyketide synthases (PKSs), chains are polymerized by the heterodimeric ketosynthase-chain length factor (KS-CLF). Here we present the 2.0-A structure of the actinorhodin KS-CLF, which shows polyketides being elongated inside an amphipathic tunnel approximately 17 A in length at the heterodimer interface. The structure resolves many of the questions about the roles of KS and CLF. Although CLF regulates chain length, it does not have an active site; KS must catalyze both chain initiation and elongation. We provide evidence that the first cyclization of the polyketide occurs within the KS-CLF tunnel. The mechanistic details of this central PKS polymerase could guide biosynthetic chemists in designing new pharmaceuticals and polymers.

About this Structure

1TQY is a Protein complex structure of sequences from Bacteria and Streptomyces coelicolor with , and as ligands. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Full crystallographic information is available from OCA.

Reference

An antibiotic factory caught in action., Keatinge-Clay AT, Maltby DA, Medzihradszky KF, Khosla C, Stroud RM, Nat Struct Mol Biol. 2004 Sep;11(9):888-93. Epub 2004 Aug 1. PMID:15286722

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