Nature Structural Biology
3, 188 - 192 (1996)
doi:10.1038/nsb0296-188
Evidence for a double-helical structure for modular polyketide synthasesJames Staunton1, Patrick Caffrey2, Jesús F. Aparicio2, Gareth A. Roberts3, Susanne S. Bethell4
& Peter F. Leadlay2
1University Chemical Laboratory University of Cambridge Lensfield Road Cambridge CB2 1EW, UK
2Department of Biochemistry University of Cambridge Tennis Court Road Cambridge CB2 1QW,UK
3National Institute for Medical Research The Ridgeway Mill Hill London NW7 1AA, UK
4Department of Biomolecular Structure Glaxo Wellcome Research and Development Ltd Gunnels Wood Road Stevenage, Hartfordshire SG1 2NY, UK Modular polyketide synthases are multienzymes responsible for the biosynthesis of a large number of clinically important natural products. They contain multiple sets, or modules, of enzymatic activities, distributed between a few giant multienzymes and there is one module for every successive cycle of polyketide chain extension. We show here that each multi-enzyme in a typical modular polyketide synthase forms a (possibly helical) parallel dimer, and that each pair of identical modules interacts closely across the dimer interface. Such an arrangement would allow identical modules to share active sites for chain extension, and thus to function independently of flanking modules, which would have important implications both for mechanisms of evolution of polyketide synthases and for their future genetic engineering.
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