Active-site residue, domain and module swaps in modular polyketide synthases.
Sequence comparisons of multiple acyltransferase (AT) domains from modular polyketide synthases (PKSs) have highlighted a correlation between a short sequence motif and the nature of the extender unit selected. When this motif was specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora erythraea, the products included triketide lactones in which acetate extension units had been incorporated instead of propionate units at the predicted positions. We also describe a cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and demonstrate its use in domain and module swaps.
Del Vecchio
Francesca
F
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, UK.
Petkovic
Hrvoje
H
Kendrew
Steven G
SG
Low
Lindsey
L
Wilkinson
Barrie
B
Lill
Rachel
R
Cortés
Jesús
J
Rudd
Brian A M
BA
Staunton
Jim
J
Leadlay
Peter F
PF
D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001665:Binding Sites; D004917:Erythromycin / Q000096:biosynthesis; D007218:Industrial Microbiology; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D016930:Saccharopolyspora / Q000201:enzymology* / Q000235:genetics; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D015645:Tylosin / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D009097:Multienzyme Complexes; D004917:Erythromycin; D015645:Tylosin