title: Active-site residue, domain and module swaps in modular polyketide synthases.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Del Vecchio
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Petkovic
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kendrew
authors.forename: Lindsey
authors.initials: L
authors.lastname: Low
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Rachel
authors.initials: R
authors.lastname: Lill
authors.forename: Jesús
authors.initials: J
authors.lastname: Cortés
authors.forename: Brian A M
authors.initials: BA
authors.lastname: Rudd
authors.forename: Jim
authors.initials: J
authors.lastname: Staunton
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D009097:Multienzyme Complexes; D004917:Erythromycin; D015645:Tylosin