Evidence for a double-helical structure for modular polyketide synthases.
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 multienzyme 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.
Staunton
J
J
University Chemical Laboratory, University of Cambridge, UK.
Caffrey
P
P
Aparicio
J F
JF
Roberts
G A
GA
Bethell
S S
SS
Leadlay
P F
PF
D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D016930:Saccharopolyspora / Q000201:enzymology
D009097:Multienzyme Complexes; D010446:Peptide Fragments