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- Title
An antibiotic factory caught in action.
- Authors
Keatinge-Clay, Adrian T.; Maltby, David A.; Medzihradszky, Katalin F.; Khosla, Chaitan; Stroud, Robert M.
- Abstract
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-Å structure of the actinorhodin KS-CLF, which shows polyketides being elongated inside an amphipathic tunnel ~17 Å 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.
- Subjects
POLYKETIDES; KETENES; OXO compounds; POLYMERS; ENZYME kinetics; ENZYMES
- Publication
Nature Structural & Molecular Biology, 2004, Vol 11, Issue 9, p888
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb808